Accumulating evidence has demonstrated the involvement of B cells in neuroinflammation and neuroregeneration.However,the role of B cells in ischemic stroke remains unclear.In this study,we identified a novel phenotype...Accumulating evidence has demonstrated the involvement of B cells in neuroinflammation and neuroregeneration.However,the role of B cells in ischemic stroke remains unclear.In this study,we identified a novel phenotype of macrophage-like B cells in brain-infiltrating immune cells expressing a high level of CD45.Macrophage-like B cells chara cterized by co-expression of B-cell and macrophage markers,showed stronger phagocytic and chemotactic functions compared with other B cells and showed upregulated expression of phagocytosis-related genes.Gene Ontology analysis found that the expression of genes associated with phagocytosis,including phagosome-and lysosome-related genes,was upregulated in macrophage-like B cells.The phagocytic activity of macrophage-like B cells was ve rified by immunostaining and three-dimensional reconstruction,in which TREM2-labeled macrophage-like B cells enwrapped and internalized myelin debris after cerebral ischemia.Cell-cell interaction analysis revealed that macrophage-like B cells released multiple chemokines to recruit peripheral immune cells mainly via CCL pathways.Single-cell RNA sequencing showed that the transdiffe rentiation to macrophage-like B cells may be induced by specific upregulation of the transcription factor CEBP fa mily to the myeloid lineage and/or by downregulation of the transcription factor Pax5 to the lymphoid lineage.Furthermore,this distinct B cell phenotype was detected in brain tissues from mice or patients with traumatic brain injury,Alzheimer’s disease,and glioblastoma.Overall,these results provide a new perspective on the phagocytic capability and chemotactic function of B cells in the ischemic brain.These cells may serve as an immunotherapeutic target for regulating the immune response of ischemic stroke.展开更多
Background:Dihydroartemisinin(DHA)is reported to be a potential anticancer agent,and the mechanisms underlying the effects of DHA on diffuse large B cell lymphoma however are still obscure.This study aimed to assess t...Background:Dihydroartemisinin(DHA)is reported to be a potential anticancer agent,and the mechanisms underlying the effects of DHA on diffuse large B cell lymphoma however are still obscure.This study aimed to assess the antitumor effect of DHA on diffuse large B cell lymphoma cells and to determine the potential underlying mechanisms of DHA-induced cell apoptosis.Methods:Here,the Cell Counting Kit 8 assay was conducted to study cell proliferation.We performed Annexin V-FITC/propidium iodide staining,real-time polymerase chain reaction,and western blot analysis to analyze cell apoptosis and potential molecular mechanisms.Results:The results showed that DHA substantially suppressed cell proliferation and induced cell apoptosis in vitro in a time-and concentration-dependent fashion.Moreover,STAT3 activity could be inhibited after stimulation with DHA.Conclusion:These results imply that the underlying anti-tumoral effect of DHA may increase apoptosis in diffuse large B cell lymphoma cells via the STAT3 signaling pathway.In addition,DHA might be an effective drug for diffuse large B cell lymphoma therapy.展开更多
BACKGROUND Recent evidence has indicated the role of B cells and B cell-activating factor(BAFF)in the development of hepatocellular carcinoma(HCC).AIM To characterize circulating BAFF receptor expression and B cell su...BACKGROUND Recent evidence has indicated the role of B cells and B cell-activating factor(BAFF)in the development of hepatocellular carcinoma(HCC).AIM To characterize circulating BAFF receptor expression and B cell subpopulations in patients with hepatitis B virus(HBV)-related HCC.METHODS Peripheral blood samples collected from 41 patients with chronic HBV infection(25 patients without HCC and 16 patients with HCC)and 9 healthy controls were assessed for BAFF receptors[BAFF-R(B cell-activating factor receptor),transmembrane activator and cyclophilin ligand interactor,B-cell maturation antigen]and B cell subpopulations by multicolor flow cytometry.RESULTS The frequency of BAFF-R expressing B cells to total B cells was significantly lower in patients with HCC(3.39%±2.12%)compared with the non-HCC group(5.37%±1.90%)and healthy controls(6.23%±2.32%),whereas there was no difference in transmembrane activator and cyclophilin ligand interactor and Bcell maturation antigen.The frequencies of CD27+Ig D+memory B cells,CD27+Ig Dclass-switched memory B cells and plasmablasts were significantly lower in the patients with HCC compared to patients without HCC(1.23±1.17 vs 3.09±1.55,P=0.001,0.60±0.44 vs 1.69±0.86,P<0.0001 and 0.16±0.12 vs 0.37±0.30,P=0.014,respectively).However,the ratio of na?ve and transitional B cell did not differ significantly between the three groups.In addition,decreased BAFF-R expression on B cells was significantly correlated with large tumor size and advanced tumor stage.CONCLUSION Our data demonstrated BAFF-R expression was reduced in B cells that involved with the frequencies of B cells maturation in patients with HCC.The depletion of BAFF-R might play an important role in the development of HCC in patients with chronic HBV infection.展开更多
AIM:To evaluate retrospectively the efficacy of rituximab plus chemotherapy in gastric diffuse large B cell lymphoma(DLBCL).METHODS:Sixty patients(median age:58 years)with histologically confirmed gastric DLBCL treate...AIM:To evaluate retrospectively the efficacy of rituximab plus chemotherapy in gastric diffuse large B cell lymphoma(DLBCL).METHODS:Sixty patients(median age:58 years)with histologically confirmed gastric DLBCL treated at four Italian institutions between 2000 and 2007,were included in this analysis.Patients were selected by stage (Ⅰ-Ⅳ,Lugano staging system),European Cooperative Oncology Group performance status(0-2)and treatment strategies.Treatment strategies were chemotherapy alone(group A,n=30)[scheduled as cyclophosphamide,doxorubicin,vincristine and prednisone (CHOP)and CHOP-like],and chemotherapy combined with rituximab(group B,n=30).The primary end point of the study was complete response(CR)rate;the secondary end points were disease-free survival (DFS)at 5 years and overall survival(OS).RESULTS:Median follow-up was 62 mo(range:31102 mo).We observed a significant difference between the two groups(A vs B)in terms of CR[76.6%(23/30) vs 100%,P=0.04)and DFS at 5 years[73.3%(22/30) vs 100%,P=0.03).To date,19 group A(63.3%) patients are alive and 11 have died,while all group B patients are alive.No significant differences in toxicity were observed between the two groups.CONCLUSION:Rituximab in combination with chemotherapy improves CR rate,DFS and OS.Further prospective trials are needed to confirm our results.展开更多
Objective: There is heterogeneity in the prognosis of gastric cancers staged according to the tumornodes-metastasis(TNM) system.This study evaluated the prognostic potential of an immune score system to supplement the...Objective: There is heterogeneity in the prognosis of gastric cancers staged according to the tumornodes-metastasis(TNM) system.This study evaluated the prognostic potential of an immune score system to supplement the TNM staging system.Methods: An immunohistochemical analysis was conducted to assess the density of T cells, B cells, and myeloid-derived suppressor cells(MDSCs) in cancer tissues from 100 stage ⅢA gastric cancer patients; the expression of the high-mobility group protein B1(HMGB1) was also evaluated in cancer cells.The relationship between the overall survival(OS), disease-free survival(DFS), and immunological parameters was analyzed.Results: An immune score system was compiled based on the prognostic role of the density of T cells, B cells, MDSCs, and the expression of HMGB1 in cancer tissues.The median 5-year survival of this group of patient was 32%.However, the 5-year survival rates of 80.0%, 51.7%, 0%, 5.8%, and 0% varied among the patients with an immune score of 4 to those with an immune score of 0 based on the immune score system, respectively.Similarly, differences in DFS rates were observed among the immune score subgroups.Conclusions: An immune score system could effectively identify the prognostic heterogeneity within stage ⅢA gastric cancer patients, implying that this immune score system may potentially supplement the TNM staging system, and help in identifying a more homogeneous group of patients who on the basis of prognosis can undergo adjuvant therapy.展开更多
AIM: To investigate the association between IL-10-producing regulatory B(B10) cells and the clinical features of thyroid-associated orbitopathy(TAO). METHODS: A total of 30 patients with TAO were recruited at Zhongsha...AIM: To investigate the association between IL-10-producing regulatory B(B10) cells and the clinical features of thyroid-associated orbitopathy(TAO). METHODS: A total of 30 patients with TAO were recruited at Zhongshan Ophthalmic Center from May 2015 to December 2015. Peripheral blood mononuclear cells(PBMCs) were separated from blood samples of 30 TAO patients and 16 healthy controls and stimulated with CD40 ligand and CpG for 48h. The frequency of IL-10^+ B cells was examined by flow cytometry and the correlation between the frequency of IL-10^+ B cells and clinical features of TAO was analyzed by SPSS. RESULTS: The frequency of IL-10^+ B cells among CD19^+ B cells in TAO patients was significantly lower than in healthy controls(TAO: 4.66%±1.88% vs healthy control: 6.82%±2.40%, P<0.01). The frequency of IL-10^+ B cells showed a positive correlation with disease activity of TAO measured by Clinical Activity Score(CAS)(r=0.50, P<0.01), and became higher in TAO patients with family history of Graves' disease(GD)(P=0.04). CONCLUSION: The decrease of the frequency of IL-10^+ B cells in TAO patients indicates the deficiency of B10 cells in TAO, and the positive association with disease activity suggests its important role in TAO inflammation regulation.展开更多
Multiple myeloma(MM) is the second most common hematologic malignancy, and is characterized by the clonal expansion of malignant plasma cells. Despite the recent improvement in patient outcome due to the use of novel ...Multiple myeloma(MM) is the second most common hematologic malignancy, and is characterized by the clonal expansion of malignant plasma cells. Despite the recent improvement in patient outcome due to the use of novel therapeutic agents and stem cell transplantation, all patients eventually relapse due to clone evolution. B cell maturation antigen(BCMA) is highly expressed in and specific for MM cells, and has been implicated in the pathogenesis as well as treatment development for MM. In this review, we will summarize representative anti-BCMA immune therapeutic strategies, including BCMA-targeted vaccines, anti-BCMA antibodies and BCMA-targeted CAR cells. Combination of different immunotherapeutic strategies of targeting BCMA, multi-target immune therapeutic strategies, and adding immune modulatory agents to normalize anti-MM immune system in minimal residual disease(MRD) negative patients, will also be discussed.展开更多
Objective:Several studies indicated that tonsillectomy can improve the prognosis of patients with immunoglobulin A nephropathy(IgAN).However,the relationship between tonsillar immunity and IgAN is still unclear.Method...Objective:Several studies indicated that tonsillectomy can improve the prognosis of patients with immunoglobulin A nephropathy(IgAN).However,the relationship between tonsillar immunity and IgAN is still unclear.Methods:A total of 14 IgAN patients were recruited in the current study from May 2015 to April 2016 in Tongji Hospital.B cells,dendritic cells(DCs),and IgAl positive cells in human tonsils were detected using immunofluorescence and immunohistochemistry.Correlations between these cells and clinicopathologic features were evaluated.展开更多
BACKGROUND Antisynthetase syndrome(ASS)is characterized by the presence of antisynthetase antibodies coupled with clinical findings such as fever,polymyositis-dermatomyositis and interstitial lung disease.It is,howeve...BACKGROUND Antisynthetase syndrome(ASS)is characterized by the presence of antisynthetase antibodies coupled with clinical findings such as fever,polymyositis-dermatomyositis and interstitial lung disease.It is,however,rare to observe ASS association with B cell lymphoma presenting severe pneumonia as the first clinical manifestation.CASE SUMMARY We evaluated a 59-year-old male patient who presented with cough with sputum,shortness of breath and fever for 13 d.A chest computed tomography radiograph revealed bilateral diffuse ground-glass infiltrates in both upper fields,left lingual lobe and right middle lobe.Initially,the patient was diagnosed with severe community-acquired pneumonia and respiratory failure.He was empirically treated with broad-spectrum antibiotics,without improvement.Further analysis showed an ASS panel with anti-PL7 antibodies.Besides,electromyography evaluation demonstrated a manifestation of myogenic damage,while deltoid muscle biopsy showed irregular muscle fiber bundles especially abnormal lymphocyte infiltration.In addition,bone marrow biopsy revealed high invasive B cell lymphoma.Thus,the patient was diagnosed with a relatively rare anti–PL7 antibody positive ASS associated with B cell lymphoma.CONCLUSION This case highlights that rapidly progressive lung lesions and acute hypoxemic respiratory failure associated with heliotrope rash and extremely high lactate dehydrogenase level should be considered as the characteristics of non-infectious diseases,especially ASS and B cell lymphoma.展开更多
BACKGROUND Immune dysfunction is the crucial cause in the pathogenesis of inflammatory bowel disease(IBD),which is mainly related to lymphocytes(T or B cells,including memory B cells),mast cells,activated neutrophils,...BACKGROUND Immune dysfunction is the crucial cause in the pathogenesis of inflammatory bowel disease(IBD),which is mainly related to lymphocytes(T or B cells,including memory B cells),mast cells,activated neutrophils,and macrophages.As the precursor of B cells,the activation of memory B cells can trigger and differentiate B cells to produce a giant variety of inducible B cells and tolerant B cells,whose dysfunction can easily lead to autoimmune diseases,including IBD.AIM To investigate whether or not curcumin(Cur)can alleviate experimental colitis by regulating memory B cells and Bcl-6-Syk-BLNK signaling.METHODS Colitis was induced in mice with a dextran sulphate sodium(DSS)solution in drinking water.Colitis mice were given Cur(100 mg/kg/d)orally for 14 consecutive days.The colonic weight,colonic length,intestinal weight index,occult blood scores,and histological scores of mice were examined to evaluate the curative effect.The levels of memory B cells in peripheral blood of mice were measured by flow cytometry,and IL-1β,IL-6,IL-10,IL-7A,and TNF-αexpression in colonic tissue homogenates were analyzed by enzyme-linked immunosorbent assay.Western blot was used to measure the expression of Bcl-6,BLNK,Syk,and other signaling pathway related proteins.RESULTS After Cur treatment for 14 d,the body weight,colonic weight,colonic length,colonic weight index,and colonic pathological injury of mice with colitis were ameliorated.The secretion of IL-1β,IL-6,TNF-α,and IL-7A was statistically decreased,while the IL-35 and IL-10 levels were considerably increased.Activation of memory B cell subsets in colitis mice was confirmed by a remarkable reduction in the expression of IgM,IgG,IgA,FCRL5,CD103,FasL,PD-1,CD38,and CXCR3 on the surface of CD19^(+)CD27^(+)B cells,while the number of CD19^(+)CD27^(+)IL-10^(+)and CD19^(+)CD27^(+)Tim-3^(+)B cells increased significantly.In addition,Cur significantly inhibited the protein levels of Syk,p-Syk,Bcl-6,and CIN85,and increased BLNK and p-BLNK expression in colitis mice.CONCLUSION Cur could effectively alleviate DSS-induced colitis in mice by regulating memory B cells and the Bcl-6-Syk-BLNK signaling pathway.展开更多
Pancreatic cancer is a disease with high unmet clinical need.Pancreatic cancer is also characterised by an intense fibrotic stroma,which harbours many immune cells.Studies in both human and animal models have demonstr...Pancreatic cancer is a disease with high unmet clinical need.Pancreatic cancer is also characterised by an intense fibrotic stroma,which harbours many immune cells.Studies in both human and animal models have demonstrated that the immune system plays a crucial role in modulating tumour onset and progression.In human pancreatic ductal adenocarcinoma,high B-cell infiltration correlates with better patient survival.Hence,B cells have received recent interest in pancreatic cancer as potential therapeutic targets.However,the data on the role of B cells in murine models is unclear as it is dependent on the pancreatic cancer model used to study.Nevertheless,it appears that B cells do organise along with other immune cells such as a network of follicular dendritic cells(DCs),surrounded by T cells and DCs to form tertiary lymphoid structures(TLS).TLS are increasingly recognised as sites for antigen presentation,T-cell activation,Bcell maturation and differentiation in plasma cells.In this review we dissect the role of B cells and provide directions for future studies to harness the role of B cells in treatment of human pancreatic cancer.展开更多
Although chimeric antigen receptor-modified(CAR)T cell therapy has been successfully applied in the treatment of acute B lymphocytic leukemia,its effect on Burkitt lymphoma(BL)and chronic B lymphocytic leukemia(B-CLL)...Although chimeric antigen receptor-modified(CAR)T cell therapy has been successfully applied in the treatment of acute B lymphocytic leukemia,its effect on Burkitt lymphoma(BL)and chronic B lymphocytic leukemia(B-CLL)is unsatisfactory.Moreover,fatal side effects greatly impede CAR T cell application.Extracellular vesicles(EVs)are excellent carriers of therapeutic agents.Nevertheless,EVs mainly accumulate in the liver when administered without modification.As an envelope glycoprotein of Epstein–Barr viruses,gp350 can efficiently bind CD21 on B cells.Here,gp350 was directly anchored onto red blood cell EVs(RBC-EVs)via its transmembrane region combined with low-voltage electroporation.The results showed that gp350 could anchor to RBC-EVs with high efficiency and that the resulting gp350-anchored RBC-EVs(RBC-EVs/gp350^(Etp))exhibited increased targeting to CD21+BL and B-CLL relative to RBC-EVs.After the loading of doxorubicin or fludarabine,RBC-EVs/gp350^(Etp) had powerful cytotoxicity and therapeutic efficacy on CD21+BL or B-CLL,respectively.Moreover,RBC-EVs/gp350^(Etp) loaded with a drug did not exhibit any apparent systemic toxicity and specifically induced the apoptosis of tumor B cells but not normal Bcells.Therefore,our findings indicate that drug-loaded RBC-EVs/gp350^(Etp) may be adopted in the treatment of CD21+B cell malignancies.展开更多
BACKGROUND Central nervous system(CNS)lesions and peripheral neuropathy are rare among patients with non-Hodgkin’s lymphoma(NHL).Lymphomatous infiltration or local oppression usually accounts for CNS or peripheral ne...BACKGROUND Central nervous system(CNS)lesions and peripheral neuropathy are rare among patients with non-Hodgkin’s lymphoma(NHL).Lymphomatous infiltration or local oppression usually accounts for CNS or peripheral nerve lesions.The incidence of peripheral neuropathy was 5%.Guillain-Barrésyndrome(GBS)is rare and may occur in less than 0.3%of patients with NHL.Hemophagocytic syndrome(HPS)is a rare complication of NHL.It has been reported that 1%of patients with hematological malignancies develop HPS.Diffuse large B-cell lymphoma(DLBCL)combined with GBS has been reported in 10 cases.CASE SUMMARY We report the case of a 53-year-old man who was initially hospitalized because of abnormal feelings in the lower limbs and urinary incontinence.He was finally diagnosed with DLBCL combined with GBS and HPS after 16 d,which was earlier than previously reported.Immunoglobulin pulse therapy,dexamethasone,and etoposide were immediately administered.The neurological symptoms did not improve,but cytopenia was relieved.However,GBS-related clinical symptoms were relieved partially after one cycle of rituximab-cyclophosphamide,hydroxydaunorubicin,vincristine,and prednisone(R-CHOP)chemotherapy and disappeared after six cycles of R-CHOP.CONCLUSION GBS and HPS heralding the diagnosis of Epstein-Barr virus DLBCL are rare.Herein,we report a rare case of DLBCL combined with GBS and HPS,and share our clinical experience.Traditional therapies may be effective if GBS occurs before lymphoma is diagnosed.Rapid diagnosis and treatment of DLBCL are crucial.展开更多
BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is the most common type of malignant lymphoma(ML),accounting for 30%-40%of cases of non-Hodgkin’s lymphoma(NHL)in adults.Primary paranasal sinus lymphoma is a rare prese...BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is the most common type of malignant lymphoma(ML),accounting for 30%-40%of cases of non-Hodgkin’s lymphoma(NHL)in adults.Primary paranasal sinus lymphoma is a rare presentation of extranodal NHL that accounts for only 0.17%of all lymphomas.ML from the maxillary sinus(MS)is a particularly rare presentation,and is thus often difficult to diagnose.We have reported the first known case of DLBCL originating from the MS with rapidly occurrent multiple skin metastasis.CASE SUMMARY An 81-year-old Japanese man visited our hospital due to continuous pain for 12 d in the left maxillary nerve area.His medical history included splenectomy due to a traffic injury,an old right cerebral infarction from when he was 74-years-old,hypertension,and type 2 diabetes mellitus.A plain head computed tomography(CT)scan revealed a 3 cm×3.1 cm×3 cm sized left MS.On day 25,left diplopia and ptosis occurred,and a follow-up CT on day 31 revealed the growth of the left MS mass.Based on an MS biopsy on day 50,we established a definitive diagnosis of DLBCL,non-germinal center B-cell-like originating from the left MS.The patient was admitted on day 62 due to rapid deterioration of his condition,and a plain CT scan revealed the further growth of the left MS mass,as well as multiple systemic metastasis,including of the skin.A skin biopsy on day 70 was found to be the same as that of the left MS mass.We notified the patient and his family of the disease,and they opted for palliative care,considering on his condition and age.The patient died on day 80.CONCLUSION This case suggests the need for careful,detailed examination,and for careful follow-up,when encountering patients presenting with a mass.展开更多
BACKGROUNDOver the past 20 years,we have gained a deep understanding of the biologicalheterogeneity of diffuse large B cell lymphoma(DLBCL)and have developed arange of new treatment programs based on the characteristi...BACKGROUNDOver the past 20 years,we have gained a deep understanding of the biologicalheterogeneity of diffuse large B cell lymphoma(DLBCL)and have developed arange of new treatment programs based on the characteristics of the disease,bringing us to the era of immune-chemotherapy.However,the effectiveness andmolecular mechanisms of targeted-immunotherapy remain unclear in DLBCL.Targeted-immunotherapy may be beneficial for specific subgroups of patients,thus requiring biomarker assessment.CASE SUMMARYHere,we report a case of MCD subtype DLBCL with MYD88L265P and CD79Bmutations,considered in the initial stage as lymphoplasmic lymphoma(LPL)orWaldenstrom macroglobulinemia(WM).Flow cytometry supported this view;however,the immunohistochemical results of the lymph nodes overturned theabove diagnosis,and the patient was eventually diagnosed with MCD subtypeDLBCL.The presence of a monoclonal IgM component in the serum and infiltrationof small lymphocytes with a phenotype compatible with WM into the bonemarrow led us to propose a hypothesis that the case we report may have transformedfrom LPL/WM.CONCLUSIONThis highlights the possible transformation from WM to DLBCL,CD79B mutationmay be a potential biomarker for predicting this conversion.展开更多
Immunoglobulin (Ig) M production can be induced by the interaction of thymus-independent type-2 (TI-2) antigen (Ag) with B cell Ag receptors (BCRs) without the involvement of conventional T cells;for IgG production th...Immunoglobulin (Ig) M production can be induced by the interaction of thymus-independent type-2 (TI-2) antigen (Ag) with B cell Ag receptors (BCRs) without the involvement of conventional T cells;for IgG production through the same process, however, a second signal is required. Previous studies have reported that invariant natural killer T (iNKT) cells may be responsible for the second signal involved in IgG production. In the present study, we addressed whether human iNKT cells could participate in the production of Ig against TI-2 Ag in vitro. Two major distinct subsets of human iNKT cells, CD4<sup>+</sup> CD8β<sup>-</sup> (CD4) and CD4<sup>-</sup> CD8β<sup>-</sup> [double negative (DN)] cells, were generated from peripheral blood monocytes from a healthy volunteer. BCR engagement, triggered by anti-IgM antibody stimulation, examined here as a model of BCR engagement triggered by TI-2 Ag, induced abundant IgM production by B cells. Both CD4 and DN iNKT cells reduced IgM production and conversely enhanced IgG production in a dose-dependent manner. In addition, IgG production by CD19<sup>+</sup>CD27<sup>-</sup> (naïve) and CD19<sup>+</sup>CD27<sup>+</sup> (memory) B cells was predominantly promoted by DNiNKT cells rather than CD4 iNKT cells;nevertheless, IgM production by both B cell subsets was similarly reduced by either subset of iNKT cells. These results suggest that the DN iNKT subsets may preferentially promote Ig class switching by B cells upon stimulation with TI-2 Ag.展开更多
B cells play immunomodulatory roles mainly by presenting antigens and producing antibodies. In recent years, some B cells were shown to exhibit regulatory functions. This type of B cell was named regulatory B cells(Br...B cells play immunomodulatory roles mainly by presenting antigens and producing antibodies. In recent years, some B cells were shown to exhibit regulatory functions. This type of B cell was named regulatory B cells(Bregs). Bregs can mediate immune tolerance to inhibit excessive inflammatory responses and to accelerate recovery of infl ammation by producing interleukin 10 and/or transforming growth factor β1 and other inhibitory cytokines. Studies showed that Bregs play important roles in parasites, bacteria, and viral infections. This study reviews biological characteristics, functions, and microsignal regulation of Bregs and their mechanism in infectious diseases and related research progress.展开更多
Background:The study of regulatory B cells(Bregs)in systemic lupus erythematosus(SLE)has been in full swing in recent years,but the number and function of Bregs in SLE patients have also present quite contradictory re...Background:The study of regulatory B cells(Bregs)in systemic lupus erythematosus(SLE)has been in full swing in recent years,but the number and function of Bregs in SLE patients have also present quite contradictory results.Therefore,we conducted a meta-analysis to verify the changes in Bregs in active SLE.Methods:We identified studies reporting the proportions of Bregs in SLE patients by searching Pubmed,Embase,Web of Science,Cochrane and CNKI.Due to the degree of heterogeneity is very high,we used a random effects model to assess the mean differences in percentages of Bregs between active SLE and controls.Then,sensitivity analysis and subgroup analysis were performed to verify potential sources of heterogeneity.Results:Seven eligible articles involving 301 active SLE patients and 218 controls were included in the meta-analysis.The pooled percentages of Bregs were found no significant difference between active SLE patients and healthy controls[0.259,(−1.150,1.668),p=0.719],with great heterogeneity(I2=97.5%).The result of sensitivity analysis showed that exclusion of any single study or single article did not materially resolve the heterogeneity,but after excluding the article conducted by Cai X and his colleagues,the percentages of Bregs were significantly higher in active SLE than those in controls[1.394,(0.114,2.675),p=0.033].The results of subgroup analysis revealed that when the disease activity was judged by SLEDAI score≥5,the percentages of Bregs were significantly lower in the SLE groups than in the control groups[-1.99,(-3.241,-0.739),p=0.002],but when the threshold of SLEDAI score≥6 chosen for active SLE,the percentages of Bregs were significantly increased in the SLE groups[2.546,(1.333,3.759),p<0.001].Meanwhile,other subgroup analysis based on the different phenotypes of Bregs,diagnostic criteria,enrolled research countries,treatment status,and organ involvement did not differ in proportion of Bregs between SLE patients and controls.Conclusions:The study implies that Bregs may play a role in the pathogenesis of active SLE,and the thresholds of SLEDAI score to distinguish between active and inactive SLE patients are important factors affecting the percentages of Bregs.展开更多
Background: B-cell Acute lymphoblastic leukemia (B-ALL) is a neoplasm of lymphoblasts which are of B-cell lineage typically composed of small to medium sized blast cells, moderately condensed to dispersed chromatin wi...Background: B-cell Acute lymphoblastic leukemia (B-ALL) is a neoplasm of lymphoblasts which are of B-cell lineage typically composed of small to medium sized blast cells, moderately condensed to dispersed chromatin with scanty cytoplasm and inconspicuous nucleoli, involving the bone marrow and/or blood. Methods and materials: This is a prospective cross-sectional study in which 50 blood and/or bone marrow samples of newly diagnosed patients (B-ALL) were tested for immunophenotyping. All samples were prepared for surface and cytoplasmic markers including kappa and lambda human antibody for 10 minutes in dark place and then run by the Flow Cytometer. Results: 64% of the study populations were males and 36% were females. Cases were classified according to immunophenotype and the age into different subtypes and showed the following frequencies: Pro B-ALL (8%), early pre B-ALL (56%), common B-ALL (16%), Pre-B-ALL (14%) and Mature B-ALL (only 6%). Surface immunoglobulin was positive in 10% and negative in 90% of all patients, showing 100% positivity in mature B-ALL and totally negative in other subtypes. While cytoplasmic immunoglobulin was positive in 16% and negative in 84% of all patients and was positive in 100% of Pre-B-ALL and in 50% of mature B-ALL. Surface kappa was more expressed in mature B-ALL than lambda giving a ratio of 2:1, while cytoplasmic kappa:lambda was 6:1 in Pre-B-ALL. Conclusion: Kappa and lambda have important role in B-ALL classification which necessitates their presence in immunophenotyping of B-ALL.展开更多
基金National Natural Science Foundation of China,No.82001460the Natural Science Foundation of Zhejiang Province,No.LQ21H250001 (both to LS)。
文摘Accumulating evidence has demonstrated the involvement of B cells in neuroinflammation and neuroregeneration.However,the role of B cells in ischemic stroke remains unclear.In this study,we identified a novel phenotype of macrophage-like B cells in brain-infiltrating immune cells expressing a high level of CD45.Macrophage-like B cells chara cterized by co-expression of B-cell and macrophage markers,showed stronger phagocytic and chemotactic functions compared with other B cells and showed upregulated expression of phagocytosis-related genes.Gene Ontology analysis found that the expression of genes associated with phagocytosis,including phagosome-and lysosome-related genes,was upregulated in macrophage-like B cells.The phagocytic activity of macrophage-like B cells was ve rified by immunostaining and three-dimensional reconstruction,in which TREM2-labeled macrophage-like B cells enwrapped and internalized myelin debris after cerebral ischemia.Cell-cell interaction analysis revealed that macrophage-like B cells released multiple chemokines to recruit peripheral immune cells mainly via CCL pathways.Single-cell RNA sequencing showed that the transdiffe rentiation to macrophage-like B cells may be induced by specific upregulation of the transcription factor CEBP fa mily to the myeloid lineage and/or by downregulation of the transcription factor Pax5 to the lymphoid lineage.Furthermore,this distinct B cell phenotype was detected in brain tissues from mice or patients with traumatic brain injury,Alzheimer’s disease,and glioblastoma.Overall,these results provide a new perspective on the phagocytic capability and chemotactic function of B cells in the ischemic brain.These cells may serve as an immunotherapeutic target for regulating the immune response of ischemic stroke.
基金supported by the Shandong Provincial Natural Science Foundation of China(ZR2019MH096).
文摘Background:Dihydroartemisinin(DHA)is reported to be a potential anticancer agent,and the mechanisms underlying the effects of DHA on diffuse large B cell lymphoma however are still obscure.This study aimed to assess the antitumor effect of DHA on diffuse large B cell lymphoma cells and to determine the potential underlying mechanisms of DHA-induced cell apoptosis.Methods:Here,the Cell Counting Kit 8 assay was conducted to study cell proliferation.We performed Annexin V-FITC/propidium iodide staining,real-time polymerase chain reaction,and western blot analysis to analyze cell apoptosis and potential molecular mechanisms.Results:The results showed that DHA substantially suppressed cell proliferation and induced cell apoptosis in vitro in a time-and concentration-dependent fashion.Moreover,STAT3 activity could be inhibited after stimulation with DHA.Conclusion:These results imply that the underlying anti-tumoral effect of DHA may increase apoptosis in diffuse large B cell lymphoma cells via the STAT3 signaling pathway.In addition,DHA might be an effective drug for diffuse large B cell lymphoma therapy.
基金Supported by the Thailand Research Fund,No.RTA6280004the Grant for Chula Research Scholar,No.CU-GRS-61-07-30-02+1 种基金Second Century Fund(C2F),Chulalongkorn Universitythe Center of Excellence in Hepatitis and Liver Cancer,Faculty of Medicine,Chulalongkorn University。
文摘BACKGROUND Recent evidence has indicated the role of B cells and B cell-activating factor(BAFF)in the development of hepatocellular carcinoma(HCC).AIM To characterize circulating BAFF receptor expression and B cell subpopulations in patients with hepatitis B virus(HBV)-related HCC.METHODS Peripheral blood samples collected from 41 patients with chronic HBV infection(25 patients without HCC and 16 patients with HCC)and 9 healthy controls were assessed for BAFF receptors[BAFF-R(B cell-activating factor receptor),transmembrane activator and cyclophilin ligand interactor,B-cell maturation antigen]and B cell subpopulations by multicolor flow cytometry.RESULTS The frequency of BAFF-R expressing B cells to total B cells was significantly lower in patients with HCC(3.39%±2.12%)compared with the non-HCC group(5.37%±1.90%)and healthy controls(6.23%±2.32%),whereas there was no difference in transmembrane activator and cyclophilin ligand interactor and Bcell maturation antigen.The frequencies of CD27+Ig D+memory B cells,CD27+Ig Dclass-switched memory B cells and plasmablasts were significantly lower in the patients with HCC compared to patients without HCC(1.23±1.17 vs 3.09±1.55,P=0.001,0.60±0.44 vs 1.69±0.86,P<0.0001 and 0.16±0.12 vs 0.37±0.30,P=0.014,respectively).However,the ratio of na?ve and transitional B cell did not differ significantly between the three groups.In addition,decreased BAFF-R expression on B cells was significantly correlated with large tumor size and advanced tumor stage.CONCLUSION Our data demonstrated BAFF-R expression was reduced in B cells that involved with the frequencies of B cells maturation in patients with HCC.The depletion of BAFF-R might play an important role in the development of HCC in patients with chronic HBV infection.
文摘AIM:To evaluate retrospectively the efficacy of rituximab plus chemotherapy in gastric diffuse large B cell lymphoma(DLBCL).METHODS:Sixty patients(median age:58 years)with histologically confirmed gastric DLBCL treated at four Italian institutions between 2000 and 2007,were included in this analysis.Patients were selected by stage (Ⅰ-Ⅳ,Lugano staging system),European Cooperative Oncology Group performance status(0-2)and treatment strategies.Treatment strategies were chemotherapy alone(group A,n=30)[scheduled as cyclophosphamide,doxorubicin,vincristine and prednisone (CHOP)and CHOP-like],and chemotherapy combined with rituximab(group B,n=30).The primary end point of the study was complete response(CR)rate;the secondary end points were disease-free survival (DFS)at 5 years and overall survival(OS).RESULTS:Median follow-up was 62 mo(range:31102 mo).We observed a significant difference between the two groups(A vs B)in terms of CR[76.6%(23/30) vs 100%,P=0.04)and DFS at 5 years[73.3%(22/30) vs 100%,P=0.03).To date,19 group A(63.3%) patients are alive and 11 have died,while all group B patients are alive.No significant differences in toxicity were observed between the two groups.CONCLUSION:Rituximab in combination with chemotherapy improves CR rate,DFS and OS.Further prospective trials are needed to confirm our results.
基金support from the National Nature Science Foundation of China ( Grant No.81272341, 81401156)Research Program of Guangzhou Municipal Health Bureau Foundation of China (Grant No.20141A011085, 20141A011088)The PhD Start-up Fund Guangzhou Medical University (Grant No.2013C49)
文摘Objective: There is heterogeneity in the prognosis of gastric cancers staged according to the tumornodes-metastasis(TNM) system.This study evaluated the prognostic potential of an immune score system to supplement the TNM staging system.Methods: An immunohistochemical analysis was conducted to assess the density of T cells, B cells, and myeloid-derived suppressor cells(MDSCs) in cancer tissues from 100 stage ⅢA gastric cancer patients; the expression of the high-mobility group protein B1(HMGB1) was also evaluated in cancer cells.The relationship between the overall survival(OS), disease-free survival(DFS), and immunological parameters was analyzed.Results: An immune score system was compiled based on the prognostic role of the density of T cells, B cells, MDSCs, and the expression of HMGB1 in cancer tissues.The median 5-year survival of this group of patient was 32%.However, the 5-year survival rates of 80.0%, 51.7%, 0%, 5.8%, and 0% varied among the patients with an immune score of 4 to those with an immune score of 0 based on the immune score system, respectively.Similarly, differences in DFS rates were observed among the immune score subgroups.Conclusions: An immune score system could effectively identify the prognostic heterogeneity within stage ⅢA gastric cancer patients, implying that this immune score system may potentially supplement the TNM staging system, and help in identifying a more homogeneous group of patients who on the basis of prognosis can undergo adjuvant therapy.
基金Supported by the National Natural Science Foundation of China(No.81470664No.81670887No.81700875)
文摘AIM: To investigate the association between IL-10-producing regulatory B(B10) cells and the clinical features of thyroid-associated orbitopathy(TAO). METHODS: A total of 30 patients with TAO were recruited at Zhongshan Ophthalmic Center from May 2015 to December 2015. Peripheral blood mononuclear cells(PBMCs) were separated from blood samples of 30 TAO patients and 16 healthy controls and stimulated with CD40 ligand and CpG for 48h. The frequency of IL-10^+ B cells was examined by flow cytometry and the correlation between the frequency of IL-10^+ B cells and clinical features of TAO was analyzed by SPSS. RESULTS: The frequency of IL-10^+ B cells among CD19^+ B cells in TAO patients was significantly lower than in healthy controls(TAO: 4.66%±1.88% vs healthy control: 6.82%±2.40%, P<0.01). The frequency of IL-10^+ B cells showed a positive correlation with disease activity of TAO measured by Clinical Activity Score(CAS)(r=0.50, P<0.01), and became higher in TAO patients with family history of Graves' disease(GD)(P=0.04). CONCLUSION: The decrease of the frequency of IL-10^+ B cells in TAO patients indicates the deficiency of B10 cells in TAO, and the positive association with disease activity suggests its important role in TAO inflammation regulation.
文摘Multiple myeloma(MM) is the second most common hematologic malignancy, and is characterized by the clonal expansion of malignant plasma cells. Despite the recent improvement in patient outcome due to the use of novel therapeutic agents and stem cell transplantation, all patients eventually relapse due to clone evolution. B cell maturation antigen(BCMA) is highly expressed in and specific for MM cells, and has been implicated in the pathogenesis as well as treatment development for MM. In this review, we will summarize representative anti-BCMA immune therapeutic strategies, including BCMA-targeted vaccines, anti-BCMA antibodies and BCMA-targeted CAR cells. Combination of different immunotherapeutic strategies of targeting BCMA, multi-target immune therapeutic strategies, and adding immune modulatory agents to normalize anti-MM immune system in minimal residual disease(MRD) negative patients, will also be discussed.
基金This project was supported by the National Natural Science Foundation of China(No.82000658,No.81770686,and No.81970591)and Huazhong University of Science and Technology research funds for self-dependent innovation(No.2017KFYXJJ101).
文摘Objective:Several studies indicated that tonsillectomy can improve the prognosis of patients with immunoglobulin A nephropathy(IgAN).However,the relationship between tonsillar immunity and IgAN is still unclear.Methods:A total of 14 IgAN patients were recruited in the current study from May 2015 to April 2016 in Tongji Hospital.B cells,dendritic cells(DCs),and IgAl positive cells in human tonsils were detected using immunofluorescence and immunohistochemistry.Correlations between these cells and clinicopathologic features were evaluated.
基金Supported by National Natural Science Foundation of China,No.81900020Natural Science Foundation of Zhejiang Province,China,No.LQ19H160020.
文摘BACKGROUND Antisynthetase syndrome(ASS)is characterized by the presence of antisynthetase antibodies coupled with clinical findings such as fever,polymyositis-dermatomyositis and interstitial lung disease.It is,however,rare to observe ASS association with B cell lymphoma presenting severe pneumonia as the first clinical manifestation.CASE SUMMARY We evaluated a 59-year-old male patient who presented with cough with sputum,shortness of breath and fever for 13 d.A chest computed tomography radiograph revealed bilateral diffuse ground-glass infiltrates in both upper fields,left lingual lobe and right middle lobe.Initially,the patient was diagnosed with severe community-acquired pneumonia and respiratory failure.He was empirically treated with broad-spectrum antibiotics,without improvement.Further analysis showed an ASS panel with anti-PL7 antibodies.Besides,electromyography evaluation demonstrated a manifestation of myogenic damage,while deltoid muscle biopsy showed irregular muscle fiber bundles especially abnormal lymphocyte infiltration.In addition,bone marrow biopsy revealed high invasive B cell lymphoma.Thus,the patient was diagnosed with a relatively rare anti–PL7 antibody positive ASS associated with B cell lymphoma.CONCLUSION This case highlights that rapidly progressive lung lesions and acute hypoxemic respiratory failure associated with heliotrope rash and extremely high lactate dehydrogenase level should be considered as the characteristics of non-infectious diseases,especially ASS and B cell lymphoma.
基金Supported by the National Natural Science Foundation of China,No.81760808Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program,No.CXTD22008.
文摘BACKGROUND Immune dysfunction is the crucial cause in the pathogenesis of inflammatory bowel disease(IBD),which is mainly related to lymphocytes(T or B cells,including memory B cells),mast cells,activated neutrophils,and macrophages.As the precursor of B cells,the activation of memory B cells can trigger and differentiate B cells to produce a giant variety of inducible B cells and tolerant B cells,whose dysfunction can easily lead to autoimmune diseases,including IBD.AIM To investigate whether or not curcumin(Cur)can alleviate experimental colitis by regulating memory B cells and Bcl-6-Syk-BLNK signaling.METHODS Colitis was induced in mice with a dextran sulphate sodium(DSS)solution in drinking water.Colitis mice were given Cur(100 mg/kg/d)orally for 14 consecutive days.The colonic weight,colonic length,intestinal weight index,occult blood scores,and histological scores of mice were examined to evaluate the curative effect.The levels of memory B cells in peripheral blood of mice were measured by flow cytometry,and IL-1β,IL-6,IL-10,IL-7A,and TNF-αexpression in colonic tissue homogenates were analyzed by enzyme-linked immunosorbent assay.Western blot was used to measure the expression of Bcl-6,BLNK,Syk,and other signaling pathway related proteins.RESULTS After Cur treatment for 14 d,the body weight,colonic weight,colonic length,colonic weight index,and colonic pathological injury of mice with colitis were ameliorated.The secretion of IL-1β,IL-6,TNF-α,and IL-7A was statistically decreased,while the IL-35 and IL-10 levels were considerably increased.Activation of memory B cell subsets in colitis mice was confirmed by a remarkable reduction in the expression of IgM,IgG,IgA,FCRL5,CD103,FasL,PD-1,CD38,and CXCR3 on the surface of CD19^(+)CD27^(+)B cells,while the number of CD19^(+)CD27^(+)IL-10^(+)and CD19^(+)CD27^(+)Tim-3^(+)B cells increased significantly.In addition,Cur significantly inhibited the protein levels of Syk,p-Syk,Bcl-6,and CIN85,and increased BLNK and p-BLNK expression in colitis mice.CONCLUSION Cur could effectively alleviate DSS-induced colitis in mice by regulating memory B cells and the Bcl-6-Syk-BLNK signaling pathway.
基金Supported by Francesca Romana Delvecchio is supported by Cancer Research UK Post-doctoral fellowshipMichelle Goulart is supported by PCRF post-doctoral fellowshipRachel Elizabeth Ann Fincham is supported by PhD studentship awarded by Barts Charity(London,UK)and A^(*)STAR(Singapore)。
文摘Pancreatic cancer is a disease with high unmet clinical need.Pancreatic cancer is also characterised by an intense fibrotic stroma,which harbours many immune cells.Studies in both human and animal models have demonstrated that the immune system plays a crucial role in modulating tumour onset and progression.In human pancreatic ductal adenocarcinoma,high B-cell infiltration correlates with better patient survival.Hence,B cells have received recent interest in pancreatic cancer as potential therapeutic targets.However,the data on the role of B cells in murine models is unclear as it is dependent on the pancreatic cancer model used to study.Nevertheless,it appears that B cells do organise along with other immune cells such as a network of follicular dendritic cells(DCs),surrounded by T cells and DCs to form tertiary lymphoid structures(TLS).TLS are increasingly recognised as sites for antigen presentation,T-cell activation,Bcell maturation and differentiation in plasma cells.In this review we dissect the role of B cells and provide directions for future studies to harness the role of B cells in treatment of human pancreatic cancer.
基金supported by the Natural Science Foundation of Zhejiang Province(LY19H160009 and LY20H120007)the National Natural Science Foundation of China(82130053,81971871,31970845 and 81901571)+1 种基金the Joint Preresearch Fund for Clinical Scientific Research of Hangzhou First People’s Hospital Affiliated to Zhejiang University(YYJJ2019Z07)the Major Project of Hangzhou Health Science and Technology Plan(Z20200134).
文摘Although chimeric antigen receptor-modified(CAR)T cell therapy has been successfully applied in the treatment of acute B lymphocytic leukemia,its effect on Burkitt lymphoma(BL)and chronic B lymphocytic leukemia(B-CLL)is unsatisfactory.Moreover,fatal side effects greatly impede CAR T cell application.Extracellular vesicles(EVs)are excellent carriers of therapeutic agents.Nevertheless,EVs mainly accumulate in the liver when administered without modification.As an envelope glycoprotein of Epstein–Barr viruses,gp350 can efficiently bind CD21 on B cells.Here,gp350 was directly anchored onto red blood cell EVs(RBC-EVs)via its transmembrane region combined with low-voltage electroporation.The results showed that gp350 could anchor to RBC-EVs with high efficiency and that the resulting gp350-anchored RBC-EVs(RBC-EVs/gp350^(Etp))exhibited increased targeting to CD21+BL and B-CLL relative to RBC-EVs.After the loading of doxorubicin or fludarabine,RBC-EVs/gp350^(Etp) had powerful cytotoxicity and therapeutic efficacy on CD21+BL or B-CLL,respectively.Moreover,RBC-EVs/gp350^(Etp) loaded with a drug did not exhibit any apparent systemic toxicity and specifically induced the apoptosis of tumor B cells but not normal Bcells.Therefore,our findings indicate that drug-loaded RBC-EVs/gp350^(Etp) may be adopted in the treatment of CD21+B cell malignancies.
文摘BACKGROUND Central nervous system(CNS)lesions and peripheral neuropathy are rare among patients with non-Hodgkin’s lymphoma(NHL).Lymphomatous infiltration or local oppression usually accounts for CNS or peripheral nerve lesions.The incidence of peripheral neuropathy was 5%.Guillain-Barrésyndrome(GBS)is rare and may occur in less than 0.3%of patients with NHL.Hemophagocytic syndrome(HPS)is a rare complication of NHL.It has been reported that 1%of patients with hematological malignancies develop HPS.Diffuse large B-cell lymphoma(DLBCL)combined with GBS has been reported in 10 cases.CASE SUMMARY We report the case of a 53-year-old man who was initially hospitalized because of abnormal feelings in the lower limbs and urinary incontinence.He was finally diagnosed with DLBCL combined with GBS and HPS after 16 d,which was earlier than previously reported.Immunoglobulin pulse therapy,dexamethasone,and etoposide were immediately administered.The neurological symptoms did not improve,but cytopenia was relieved.However,GBS-related clinical symptoms were relieved partially after one cycle of rituximab-cyclophosphamide,hydroxydaunorubicin,vincristine,and prednisone(R-CHOP)chemotherapy and disappeared after six cycles of R-CHOP.CONCLUSION GBS and HPS heralding the diagnosis of Epstein-Barr virus DLBCL are rare.Herein,we report a rare case of DLBCL combined with GBS and HPS,and share our clinical experience.Traditional therapies may be effective if GBS occurs before lymphoma is diagnosed.Rapid diagnosis and treatment of DLBCL are crucial.
文摘BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is the most common type of malignant lymphoma(ML),accounting for 30%-40%of cases of non-Hodgkin’s lymphoma(NHL)in adults.Primary paranasal sinus lymphoma is a rare presentation of extranodal NHL that accounts for only 0.17%of all lymphomas.ML from the maxillary sinus(MS)is a particularly rare presentation,and is thus often difficult to diagnose.We have reported the first known case of DLBCL originating from the MS with rapidly occurrent multiple skin metastasis.CASE SUMMARY An 81-year-old Japanese man visited our hospital due to continuous pain for 12 d in the left maxillary nerve area.His medical history included splenectomy due to a traffic injury,an old right cerebral infarction from when he was 74-years-old,hypertension,and type 2 diabetes mellitus.A plain head computed tomography(CT)scan revealed a 3 cm×3.1 cm×3 cm sized left MS.On day 25,left diplopia and ptosis occurred,and a follow-up CT on day 31 revealed the growth of the left MS mass.Based on an MS biopsy on day 50,we established a definitive diagnosis of DLBCL,non-germinal center B-cell-like originating from the left MS.The patient was admitted on day 62 due to rapid deterioration of his condition,and a plain CT scan revealed the further growth of the left MS mass,as well as multiple systemic metastasis,including of the skin.A skin biopsy on day 70 was found to be the same as that of the left MS mass.We notified the patient and his family of the disease,and they opted for palliative care,considering on his condition and age.The patient died on day 80.CONCLUSION This case suggests the need for careful,detailed examination,and for careful follow-up,when encountering patients presenting with a mass.
文摘BACKGROUNDOver the past 20 years,we have gained a deep understanding of the biologicalheterogeneity of diffuse large B cell lymphoma(DLBCL)and have developed arange of new treatment programs based on the characteristics of the disease,bringing us to the era of immune-chemotherapy.However,the effectiveness andmolecular mechanisms of targeted-immunotherapy remain unclear in DLBCL.Targeted-immunotherapy may be beneficial for specific subgroups of patients,thus requiring biomarker assessment.CASE SUMMARYHere,we report a case of MCD subtype DLBCL with MYD88L265P and CD79Bmutations,considered in the initial stage as lymphoplasmic lymphoma(LPL)orWaldenstrom macroglobulinemia(WM).Flow cytometry supported this view;however,the immunohistochemical results of the lymph nodes overturned theabove diagnosis,and the patient was eventually diagnosed with MCD subtypeDLBCL.The presence of a monoclonal IgM component in the serum and infiltrationof small lymphocytes with a phenotype compatible with WM into the bonemarrow led us to propose a hypothesis that the case we report may have transformedfrom LPL/WM.CONCLUSIONThis highlights the possible transformation from WM to DLBCL,CD79B mutationmay be a potential biomarker for predicting this conversion.
文摘Immunoglobulin (Ig) M production can be induced by the interaction of thymus-independent type-2 (TI-2) antigen (Ag) with B cell Ag receptors (BCRs) without the involvement of conventional T cells;for IgG production through the same process, however, a second signal is required. Previous studies have reported that invariant natural killer T (iNKT) cells may be responsible for the second signal involved in IgG production. In the present study, we addressed whether human iNKT cells could participate in the production of Ig against TI-2 Ag in vitro. Two major distinct subsets of human iNKT cells, CD4<sup>+</sup> CD8β<sup>-</sup> (CD4) and CD4<sup>-</sup> CD8β<sup>-</sup> [double negative (DN)] cells, were generated from peripheral blood monocytes from a healthy volunteer. BCR engagement, triggered by anti-IgM antibody stimulation, examined here as a model of BCR engagement triggered by TI-2 Ag, induced abundant IgM production by B cells. Both CD4 and DN iNKT cells reduced IgM production and conversely enhanced IgG production in a dose-dependent manner. In addition, IgG production by CD19<sup>+</sup>CD27<sup>-</sup> (naïve) and CD19<sup>+</sup>CD27<sup>+</sup> (memory) B cells was predominantly promoted by DNiNKT cells rather than CD4 iNKT cells;nevertheless, IgM production by both B cell subsets was similarly reduced by either subset of iNKT cells. These results suggest that the DN iNKT subsets may preferentially promote Ig class switching by B cells upon stimulation with TI-2 Ag.
文摘B cells play immunomodulatory roles mainly by presenting antigens and producing antibodies. In recent years, some B cells were shown to exhibit regulatory functions. This type of B cell was named regulatory B cells(Bregs). Bregs can mediate immune tolerance to inhibit excessive inflammatory responses and to accelerate recovery of infl ammation by producing interleukin 10 and/or transforming growth factor β1 and other inhibitory cytokines. Studies showed that Bregs play important roles in parasites, bacteria, and viral infections. This study reviews biological characteristics, functions, and microsignal regulation of Bregs and their mechanism in infectious diseases and related research progress.
基金This work was supported by funding from the National Natural Science Foundation of China Grants[81760286].
文摘Background:The study of regulatory B cells(Bregs)in systemic lupus erythematosus(SLE)has been in full swing in recent years,but the number and function of Bregs in SLE patients have also present quite contradictory results.Therefore,we conducted a meta-analysis to verify the changes in Bregs in active SLE.Methods:We identified studies reporting the proportions of Bregs in SLE patients by searching Pubmed,Embase,Web of Science,Cochrane and CNKI.Due to the degree of heterogeneity is very high,we used a random effects model to assess the mean differences in percentages of Bregs between active SLE and controls.Then,sensitivity analysis and subgroup analysis were performed to verify potential sources of heterogeneity.Results:Seven eligible articles involving 301 active SLE patients and 218 controls were included in the meta-analysis.The pooled percentages of Bregs were found no significant difference between active SLE patients and healthy controls[0.259,(−1.150,1.668),p=0.719],with great heterogeneity(I2=97.5%).The result of sensitivity analysis showed that exclusion of any single study or single article did not materially resolve the heterogeneity,but after excluding the article conducted by Cai X and his colleagues,the percentages of Bregs were significantly higher in active SLE than those in controls[1.394,(0.114,2.675),p=0.033].The results of subgroup analysis revealed that when the disease activity was judged by SLEDAI score≥5,the percentages of Bregs were significantly lower in the SLE groups than in the control groups[-1.99,(-3.241,-0.739),p=0.002],but when the threshold of SLEDAI score≥6 chosen for active SLE,the percentages of Bregs were significantly increased in the SLE groups[2.546,(1.333,3.759),p<0.001].Meanwhile,other subgroup analysis based on the different phenotypes of Bregs,diagnostic criteria,enrolled research countries,treatment status,and organ involvement did not differ in proportion of Bregs between SLE patients and controls.Conclusions:The study implies that Bregs may play a role in the pathogenesis of active SLE,and the thresholds of SLEDAI score to distinguish between active and inactive SLE patients are important factors affecting the percentages of Bregs.
文摘Background: B-cell Acute lymphoblastic leukemia (B-ALL) is a neoplasm of lymphoblasts which are of B-cell lineage typically composed of small to medium sized blast cells, moderately condensed to dispersed chromatin with scanty cytoplasm and inconspicuous nucleoli, involving the bone marrow and/or blood. Methods and materials: This is a prospective cross-sectional study in which 50 blood and/or bone marrow samples of newly diagnosed patients (B-ALL) were tested for immunophenotyping. All samples were prepared for surface and cytoplasmic markers including kappa and lambda human antibody for 10 minutes in dark place and then run by the Flow Cytometer. Results: 64% of the study populations were males and 36% were females. Cases were classified according to immunophenotype and the age into different subtypes and showed the following frequencies: Pro B-ALL (8%), early pre B-ALL (56%), common B-ALL (16%), Pre-B-ALL (14%) and Mature B-ALL (only 6%). Surface immunoglobulin was positive in 10% and negative in 90% of all patients, showing 100% positivity in mature B-ALL and totally negative in other subtypes. While cytoplasmic immunoglobulin was positive in 16% and negative in 84% of all patients and was positive in 100% of Pre-B-ALL and in 50% of mature B-ALL. Surface kappa was more expressed in mature B-ALL than lambda giving a ratio of 2:1, while cytoplasmic kappa:lambda was 6:1 in Pre-B-ALL. Conclusion: Kappa and lambda have important role in B-ALL classification which necessitates their presence in immunophenotyping of B-ALL.
