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
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
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
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
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
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
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
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
The defense system of teleost fish organized on innate and adaptive immunity protects them against a wide variety of pathogenic microorganisms in the aquatic environment.Phagocytosis is one of the most effective defen...The defense system of teleost fish organized on innate and adaptive immunity protects them against a wide variety of pathogenic microorganisms in the aquatic environment.Phagocytosis is one of the most effective defense strategies against microbial challenge mainly performed by classical‘professional’phagocytes(including monocytes,macrophages and granulocytes).They contain,kill and process the internalized pathogens for antigen presentation by providing antigenic ligands to initiate activation and clonal expansion of T and B cells,which bridge the innate and adaptive immunity.The discovery of phagocytic B cells in teleost fish has broken the paradigm that primary vertebrate B cells are lack of phagocytosis of particulates,as well as led to the investigation of phagocytic activity of mammalian B-1 B cells.The active phagocytic,microbicidal capabilities and antigen presentation in teleost phagocytic B cell have demonstrated to be similar as professional phagocytes,providing a potential impact on development of new vaccination strategies to prevent and control infectious diseases.In this review,we aim to address current progress on the antimicrobial role of phagocytic B cells in teleost fish by comparing it with other professional phagocytes and mammalian B-1 B cells,and provide the application prospect of phagocytic B cells in developing vaccines as well as the prevention of fish diseases.展开更多
Marginal zone(MZ)B cells,which are splenic innate-like B cells that rapidly secrete antibodies(Abs)against blood-borne pathogens,are composed of heterogeneous subpopulations.Here,we showed that MZ B cells can be divid...Marginal zone(MZ)B cells,which are splenic innate-like B cells that rapidly secrete antibodies(Abs)against blood-borne pathogens,are composed of heterogeneous subpopulations.Here,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression levels.CD80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B cells.Notably,CD80^(high)MZ B cells survived 2-Gy whole-body irradiation,whereas CD80^(low)MZ B cells were depleted by irradiation and then repleted with one month after irradiation.Depletion of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine CII.CD80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant response.CD80^(high)MZ B cells expressed more autoreactive B cell receptors(BCRs)that recognized double-stranded DNA or CII,expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences,and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80^(low)MZ B cells.Adoptive transfer experiments showed that CD21^(+)CD23^(+)transitional 2 MZ precursors preferentially generated CD80^(low)MZ B cells and that a proportion of CD80^(low)MZ B cells were converted into CD80^(high)MZ B cells;in contrast,CD80^(high)MZ B cells stably remained CD80^(high)MZ B cells.In summary,MZ B cells can be divided into two subpopulations according to their CD80 expression levels,Ab-producing capacity,radioresistance,and autoreactivity,and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.展开更多
The metabolic reprogramming underlying the generation of regulatory B cells during infectious diseases remains unknown.Using a Pseudomonas aeruginosa-induced pneumonia model,we reported that IL-10-producing B cells(IL...The metabolic reprogramming underlying the generation of regulatory B cells during infectious diseases remains unknown.Using a Pseudomonas aeruginosa-induced pneumonia model,we reported that IL-10-producing B cells(IL-10+B cells)play a key role in spontaneously resolving infection-mediated inflammation.Accumulated cytosolic reactive oxygen species(ROS)during inflammation were shown to drive IL-10+B-cell generation by remodeling one-carbon metabolism.Depletion of the enzyme serine hydroxymethyltransferase 1(Shmt1)led to inadequate one-carbon metabolism and decreased IL-10+B-cell production.Furthermore,increased one-carbon flux elevated the levels of the methyl donor S-adenosylmethionine(SAM),altering histone H3 lysine 4 methylation(H3K4me)at the Il10 gene to promote chromatin accessibility and upregulate Il10 expression in B cells.Therefore,the one-carbon metabolism-associated compound ethacrynic acid(EA)was screened and found to potentially treat infectious pneumonia by boosting IL-10+B-cell generation.Overall,these findings reveal that ROS serve as modulators to resolve inflammation by reprogramming one-carbon metabolism pathways in B cells.展开更多
Traumatic injuries in the central nervous system,such as traumatic brain injury and spinal cord injury,are associated with tissue inflammation and the infiltration of immune cells,which simultaneously affect the self-...Traumatic injuries in the central nervous system,such as traumatic brain injury and spinal cord injury,are associated with tissue inflammation and the infiltration of immune cells,which simultaneously affect the self-renewal and differentiation of neural stem cells.Howeve r,the tissue repair process instigated by endogenous neural stem cells is incapable of restoring central nervous system injuries without external intervention.Recently,resident/peripheral immune cells have been demonstrated to exert significant effects on neural stem cells.Thus,the resto ration of traumatic injuries in the central nervous system by the immune intervention in neural stem cells represents a potential therapeutic method.In this review,we discuss the roles and possible mechanisms of immune cells on the selfrenewal and differentiation of neural stem cells along with the prognosis of central nervous system injuries based on immune intervention.Finally,we discuss remaining research challenges that need to be considered in the future.Further elucidation of these challenges will fa cilitate the successful application of neural stem cells in central nervous system injuries.展开更多
Objective:To explore the balance of peripheral blood T helper 17 cells/regulatory T cell(Th17/Treg)ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans(ASO).Methods:...Objective:To explore the balance of peripheral blood T helper 17 cells/regulatory T cell(Th17/Treg)ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans(ASO).Methods:A rat model of lower extremity ASO was established,and blood samples from patients with lower extremity ASO before and after surgery were obtained.ELISA was used to detect interleukin 6(IL-6),IL-10,and IL-17.Real-time RCR and Western blot analyses were used to detect Foxp3,IL-6,IL-10,and IL-17 expression.Moreover,flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ratio.Results:Compared with the control group,the iliac artery wall of ASO rats showed significant hyperplasia,and the concentrations of cholesterol and triglyceride were significantly increased(P<0.01),indicating the successful establishment of ASO.Moreover,the levels of IL-6 and IL-17 in ASO rats were pronouncedly increased(P<0.05),while the IL-10 level was significantly decreased(P<0.05).In addition to increased IL-6 and IL-17 levels,the mRNA and protein levels of Foxp3 and IL-10 in ASO rats were significantly decreased compared with the control group.The Th17/Treg and M1/M2 ratios in the ASO group were markedly increased(P<0.05).These alternations were also observed in ASO patients.After endovascular surgery(such as percutaneous transluminal angioplasty and arterial stenting),all these changes were significantly improved(P<0.05).Conclusions:The Th17/Treg and M1/M2 ratios were significantly increased in ASO,and surgery can effectively improve the balance of Th17/Treg,and reduce the ratio of M1/M2,and the expression of inflammatory factors.展开更多
Innate lymphoid cells(ILCs)are the counterpart of T helper cells in the innate immune system and share multiple phenotypes with T helper cells.Inducible T-cell costimulator(ICOS)is recognized on T cells and participat...Innate lymphoid cells(ILCs)are the counterpart of T helper cells in the innate immune system and share multiple phenotypes with T helper cells.Inducible T-cell costimulator(ICOS)is recognized on T cells and participates in T-cell activation and T and B-cell engagement in lymphoid tissues.However,the role of ICOS in ILC3s and ILC3-involved interactions with the immune microenvironment remains unclear.Here,we found that ICOS expression on human ILC3s was correlated with the activated state of ILC3s.ICOS costimulation enhanced the survival,proliferation,and capacity of ILC3s to produce cytokines(IL-22,IL-17A,IFN-γ,TNF,and GM-CSF).Via synergistic effects of ICOS and CD40 signaling,B cells promoted ILC3 functions,and ILC3-induced T-cellindependent B-cell IgA and IgM secretion primarily required CD40 signaling.Hence,ICOS is essential for the nonredundant role of ILC3s and their interaction with adjacent B cells.展开更多
Objective:To explore the anti-melanogenic potential of Cyrtomium falcatum.Methods:The effects of Cyrtomium falcatum crude extract and its solvent fractions on tyrosinase activity,melanin content,and the expressions of...Objective:To explore the anti-melanogenic potential of Cyrtomium falcatum.Methods:The effects of Cyrtomium falcatum crude extract and its solvent fractions on tyrosinase activity,melanin content,and the expressions of melanogenesis-related genes and proteins were analyzed inα-melanocyte-stimulating hormone(α-MSH)-stimulated B16F10 cells.Results:α-MSH treatment significantly increased tyrosinase activity,and extracellular and intracellular melanin content,as well as the expression levels of tyrosinase,microphthalmia-associated transcription factor(MITF),tyrosinase-related protein(TRP)-1,and TRP-2 in B16F10 cells.Treatment with Cyrtomium falcatum crude extract and its solvent fractions reduced tyrosinase activity and extracellular and intracellular melanin content and downregulated the expression levels of tyrosinase,MITF,TRP-1,and TRP-2 in a dose-dependent manner.Conclusions:Cyrtomium falcatum has potential anti-melanogenesis effects and can be used as a potential source material in cosmeceutical industry for the research and development of novel lead molecules with whitening properties.展开更多
Evidence indicates that lung cancer development is a complex process that involves interactions between tumor cells,stromal fibroblasts,and immune cells.Tumor-infiltrating immune cells play a significant role in the p...Evidence indicates that lung cancer development is a complex process that involves interactions between tumor cells,stromal fibroblasts,and immune cells.Tumor-infiltrating immune cells play a significant role in the promotion or inhibition of tumor growth.As an integral component of the tumor microenvironment,tumor-infiltrating B lymphocytes(TIBs)exist in all stages of cancer and play important roles in shaping tumor development.Here,we review recent clinical and preclinical studies that outline the role of TIBs in lung cancer development,assess their prognostic significance,and explore the potential benefit of B cell-based immunotherapy for lung cancer treatment.展开更多
Effector B cells are central contributors to the development of autoimmune disease by activating autoreactive T cells,producing pro-inflammatory cytokines and organizing ectopic lymphoid tissue.Conversely,IL-10-produc...Effector B cells are central contributors to the development of autoimmune disease by activating autoreactive T cells,producing pro-inflammatory cytokines and organizing ectopic lymphoid tissue.Conversely,IL-10-producing regulatory B(Breg)cells have pivotal roles in maintaining immunological tolerance and restraining excessive inflammation in autoinflammatory disease.Thus,regulating the equilibrium between antibody-producing effector B cells and Breg cells is critical for the treatment of autoimmune disease.In this study,we investigated the effect of human palatine tonsil-derived mesenchymal stem cells(T-MSCs)on estradiol(E2)-induced B-cell responses in vivo and in vitro.Transplantation of T-MSC into E2-treated mice alleviated B-cell-mediated immune responses and increased the population of IL-10-producing Breg cells.T-MSCs regulated the B-cell populations by producing Epstein–Barr virus(EBV)-induced 3(EBI3),one of the two subunits of IL-35 that is the well-known inducer of Breg cells.We demonstrate a critical role of EBI3(IL-35)in vitro by depleting EBI3 in T-MSCs and by adding exogenous IL-35 to the culture system.Taken together,our data suggest that IL-35-secreting MSCs may become an attractive therapeutic to treat B-cell-mediated autoimmune diseases via expanding Breg cells.展开更多
A hallmark of systemic lupus erythematosus(SLE)is the breaking of B-cell tolerance with the generation of high-affinity autoantibodies;however,the antibody-independent features of the B-cell compartment in SLE are les...A hallmark of systemic lupus erythematosus(SLE)is the breaking of B-cell tolerance with the generation of high-affinity autoantibodies;however,the antibody-independent features of the B-cell compartment in SLE are less understood.In this study,we performed an extensive examination of B-cell subsets and their proinflammatory properties in a Chinese cohort of new-onset SLE patients.We observed that SLE patients exhibited an increased frequency of transitional B cells compared with healthy donors and rheumatoid arthritis patients.Plasma from SLE patients potently promoted the survival of transitional B cells in a type I IFN-dependent manner,which can be recapitulated by direct IFN-αtreatment.Furthermore,the effect of IFN-αon enhanced survival of transitional B cells was associated with NF-κB pathway activation and reduced expression of the pro-apoptotic molecule Bax.Transitional B cells from SLE patients harbored a higher capacity to produce proinflammatory cytokine IL-6,which was also linked to the overactivated type I IFN pathway.In addition,the frequency of IL-6-producing transitional B cells was positively correlated with disease activity in SLE patients,and these cells were significantly reduced after short-term standard therapies.Thus,the current study provides a direct link between type I IFN pathway overactivation and the abnormally high frequency and proinflammatory properties of transitional B cells in active SLE patients,which contributes to the understanding of the roles of type I IFNs and B cells in the pathogenesis of SLE.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 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.
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 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.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 the National Natural Science Foundation of China(32102827,31972818,31528019)China Postdoctoral Science Foundation(2019M662959)+1 种基金Guangdong Basic and Applied Basic Research Foundation(2019A1515110987)Special fund for promoting economic development(for modern fishery development)of Guangdong Province(grant number 2019A4).
文摘The defense system of teleost fish organized on innate and adaptive immunity protects them against a wide variety of pathogenic microorganisms in the aquatic environment.Phagocytosis is one of the most effective defense strategies against microbial challenge mainly performed by classical‘professional’phagocytes(including monocytes,macrophages and granulocytes).They contain,kill and process the internalized pathogens for antigen presentation by providing antigenic ligands to initiate activation and clonal expansion of T and B cells,which bridge the innate and adaptive immunity.The discovery of phagocytic B cells in teleost fish has broken the paradigm that primary vertebrate B cells are lack of phagocytosis of particulates,as well as led to the investigation of phagocytic activity of mammalian B-1 B cells.The active phagocytic,microbicidal capabilities and antigen presentation in teleost phagocytic B cell have demonstrated to be similar as professional phagocytes,providing a potential impact on development of new vaccination strategies to prevent and control infectious diseases.In this review,we aim to address current progress on the antimicrobial role of phagocytic B cells in teleost fish by comparing it with other professional phagocytes and mammalian B-1 B cells,and provide the application prospect of phagocytic B cells in developing vaccines as well as the prevention of fish diseases.
基金supported by National Research Foundation of Korea grant funded by the Korea government(MSIT)(2023R1A2C2004510)Korea Basic Science Institute(National Research Facilities and Equipment Center)grant(2020R1A6C101A191)of the Ministry of Education(Korea)the BK21 FOUR Program(Graduate School Innovation)of Sungkyunkwan University.
文摘Marginal zone(MZ)B cells,which are splenic innate-like B cells that rapidly secrete antibodies(Abs)against blood-borne pathogens,are composed of heterogeneous subpopulations.Here,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression levels.CD80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B cells.Notably,CD80^(high)MZ B cells survived 2-Gy whole-body irradiation,whereas CD80^(low)MZ B cells were depleted by irradiation and then repleted with one month after irradiation.Depletion of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine CII.CD80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant response.CD80^(high)MZ B cells expressed more autoreactive B cell receptors(BCRs)that recognized double-stranded DNA or CII,expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences,and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80^(low)MZ B cells.Adoptive transfer experiments showed that CD21^(+)CD23^(+)transitional 2 MZ precursors preferentially generated CD80^(low)MZ B cells and that a proportion of CD80^(low)MZ B cells were converted into CD80^(high)MZ B cells;in contrast,CD80^(high)MZ B cells stably remained CD80^(high)MZ B cells.In summary,MZ B cells can be divided into two subpopulations according to their CD80 expression levels,Ab-producing capacity,radioresistance,and autoreactivity,and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.
基金supported by the General Program of the National Natural Science Foundation of China(81971493,81771736)the Science Fund for Creative Research Groups of the National Natural Science Foundation of China(82121002)+2 种基金Major Program of National Natural Science Foundation of China(821300501,82330053)Shanghai Rising-Star Program(20QA1407900)Innovative Research Team of High-level Local Universities in Shanghai.
文摘The metabolic reprogramming underlying the generation of regulatory B cells during infectious diseases remains unknown.Using a Pseudomonas aeruginosa-induced pneumonia model,we reported that IL-10-producing B cells(IL-10+B cells)play a key role in spontaneously resolving infection-mediated inflammation.Accumulated cytosolic reactive oxygen species(ROS)during inflammation were shown to drive IL-10+B-cell generation by remodeling one-carbon metabolism.Depletion of the enzyme serine hydroxymethyltransferase 1(Shmt1)led to inadequate one-carbon metabolism and decreased IL-10+B-cell production.Furthermore,increased one-carbon flux elevated the levels of the methyl donor S-adenosylmethionine(SAM),altering histone H3 lysine 4 methylation(H3K4me)at the Il10 gene to promote chromatin accessibility and upregulate Il10 expression in B cells.Therefore,the one-carbon metabolism-associated compound ethacrynic acid(EA)was screened and found to potentially treat infectious pneumonia by boosting IL-10+B-cell generation.Overall,these findings reveal that ROS serve as modulators to resolve inflammation by reprogramming one-carbon metabolism pathways in B cells.
基金supported by the National Natural Science Foundation of China,Nos.82172527 and 81972138 (to LLW)。
文摘Traumatic injuries in the central nervous system,such as traumatic brain injury and spinal cord injury,are associated with tissue inflammation and the infiltration of immune cells,which simultaneously affect the self-renewal and differentiation of neural stem cells.Howeve r,the tissue repair process instigated by endogenous neural stem cells is incapable of restoring central nervous system injuries without external intervention.Recently,resident/peripheral immune cells have been demonstrated to exert significant effects on neural stem cells.Thus,the resto ration of traumatic injuries in the central nervous system by the immune intervention in neural stem cells represents a potential therapeutic method.In this review,we discuss the roles and possible mechanisms of immune cells on the selfrenewal and differentiation of neural stem cells along with the prognosis of central nervous system injuries based on immune intervention.Finally,we discuss remaining research challenges that need to be considered in the future.Further elucidation of these challenges will fa cilitate the successful application of neural stem cells in central nervous system injuries.
基金supported by Natural Science Foundation of Hainan Province(820MS135)Hainan Provincial Health Commission 2023 Provincial Key Clinical Discipline(Clinical Medical Center)Construction Unit Fund Project(Qiongwei Yihan[2022]No.341)Hainan Provincial Health Technology Innovation Joint Project(WSJK2024MS209).
文摘Objective:To explore the balance of peripheral blood T helper 17 cells/regulatory T cell(Th17/Treg)ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans(ASO).Methods:A rat model of lower extremity ASO was established,and blood samples from patients with lower extremity ASO before and after surgery were obtained.ELISA was used to detect interleukin 6(IL-6),IL-10,and IL-17.Real-time RCR and Western blot analyses were used to detect Foxp3,IL-6,IL-10,and IL-17 expression.Moreover,flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ratio.Results:Compared with the control group,the iliac artery wall of ASO rats showed significant hyperplasia,and the concentrations of cholesterol and triglyceride were significantly increased(P<0.01),indicating the successful establishment of ASO.Moreover,the levels of IL-6 and IL-17 in ASO rats were pronouncedly increased(P<0.05),while the IL-10 level was significantly decreased(P<0.05).In addition to increased IL-6 and IL-17 levels,the mRNA and protein levels of Foxp3 and IL-10 in ASO rats were significantly decreased compared with the control group.The Th17/Treg and M1/M2 ratios in the ASO group were markedly increased(P<0.05).These alternations were also observed in ASO patients.After endovascular surgery(such as percutaneous transluminal angioplasty and arterial stenting),all these changes were significantly improved(P<0.05).Conclusions:The Th17/Treg and M1/M2 ratios were significantly increased in ASO,and surgery can effectively improve the balance of Th17/Treg,and reduce the ratio of M1/M2,and the expression of inflammatory factors.
基金the National Key Research and Development Program(Grant 2021YFF0704800)the Science and Technology Development Program of Jilin Province(Grant 20210402009GH)+1 种基金the Science and Technology Development Program of Jilin Province(Grant YDZJ202201ZYTS098)the Norman Bethune Program of Jilin University(Grant No.2022B34).
文摘Innate lymphoid cells(ILCs)are the counterpart of T helper cells in the innate immune system and share multiple phenotypes with T helper cells.Inducible T-cell costimulator(ICOS)is recognized on T cells and participates in T-cell activation and T and B-cell engagement in lymphoid tissues.However,the role of ICOS in ILC3s and ILC3-involved interactions with the immune microenvironment remains unclear.Here,we found that ICOS expression on human ILC3s was correlated with the activated state of ILC3s.ICOS costimulation enhanced the survival,proliferation,and capacity of ILC3s to produce cytokines(IL-22,IL-17A,IFN-γ,TNF,and GM-CSF).Via synergistic effects of ICOS and CD40 signaling,B cells promoted ILC3 functions,and ILC3-induced T-cellindependent B-cell IgA and IgM secretion primarily required CD40 signaling.Hence,ICOS is essential for the nonredundant role of ILC3s and their interaction with adjacent B cells.
基金This work was supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.2023R1A2C1006268 and RS-2023-00212560).
文摘Objective:To explore the anti-melanogenic potential of Cyrtomium falcatum.Methods:The effects of Cyrtomium falcatum crude extract and its solvent fractions on tyrosinase activity,melanin content,and the expressions of melanogenesis-related genes and proteins were analyzed inα-melanocyte-stimulating hormone(α-MSH)-stimulated B16F10 cells.Results:α-MSH treatment significantly increased tyrosinase activity,and extracellular and intracellular melanin content,as well as the expression levels of tyrosinase,microphthalmia-associated transcription factor(MITF),tyrosinase-related protein(TRP)-1,and TRP-2 in B16F10 cells.Treatment with Cyrtomium falcatum crude extract and its solvent fractions reduced tyrosinase activity and extracellular and intracellular melanin content and downregulated the expression levels of tyrosinase,MITF,TRP-1,and TRP-2 in a dose-dependent manner.Conclusions:Cyrtomium falcatum has potential anti-melanogenesis effects and can be used as a potential source material in cosmeceutical industry for the research and development of novel lead molecules with whitening properties.
基金the National Natural Science Foundation of China(grant#81502202)the Canadian Cancer Society Research Institute(grant#704121)+1 种基金the China Postdoctoral Science Foundation(grant#2017M611329)the Scientific Research Project in the Science and Technology Development Plan of Jilin Province(grant#20150520142JH).
文摘Evidence indicates that lung cancer development is a complex process that involves interactions between tumor cells,stromal fibroblasts,and immune cells.Tumor-infiltrating immune cells play a significant role in the promotion or inhibition of tumor growth.As an integral component of the tumor microenvironment,tumor-infiltrating B lymphocytes(TIBs)exist in all stages of cancer and play important roles in shaping tumor development.Here,we review recent clinical and preclinical studies that outline the role of TIBs in lung cancer development,assess their prognostic significance,and explore the potential benefit of B cell-based immunotherapy for lung cancer treatment.
基金by the Bio&Medical Technology Development Program of the NRF funded by the Korean government(2012M3A9C6049823)In addition,this work was supported by RP-Grant 2016 of Ewha Womans University.
文摘Effector B cells are central contributors to the development of autoimmune disease by activating autoreactive T cells,producing pro-inflammatory cytokines and organizing ectopic lymphoid tissue.Conversely,IL-10-producing regulatory B(Breg)cells have pivotal roles in maintaining immunological tolerance and restraining excessive inflammation in autoinflammatory disease.Thus,regulating the equilibrium between antibody-producing effector B cells and Breg cells is critical for the treatment of autoimmune disease.In this study,we investigated the effect of human palatine tonsil-derived mesenchymal stem cells(T-MSCs)on estradiol(E2)-induced B-cell responses in vivo and in vitro.Transplantation of T-MSC into E2-treated mice alleviated B-cell-mediated immune responses and increased the population of IL-10-producing Breg cells.T-MSCs regulated the B-cell populations by producing Epstein–Barr virus(EBV)-induced 3(EBI3),one of the two subunits of IL-35 that is the well-known inducer of Breg cells.We demonstrate a critical role of EBI3(IL-35)in vitro by depleting EBI3 in T-MSCs and by adding exogenous IL-35 to the culture system.Taken together,our data suggest that IL-35-secreting MSCs may become an attractive therapeutic to treat B-cell-mediated autoimmune diseases via expanding Breg cells.
基金This work was supported by the National Basic Research Program of China(No.2014CB541904)the National Natural Science Foundation of China(Nos.31470879 81571575 8171101311 and 31770960)+2 种基金the Interdisciplinary Innovation Team,External Cooperation Program(No.GJHZ201312)Key Project QYZDB-SSW-SMC036the Strategic Priority Research Program(No.XDPB0303),Chinese Academy of Sciences.
文摘A hallmark of systemic lupus erythematosus(SLE)is the breaking of B-cell tolerance with the generation of high-affinity autoantibodies;however,the antibody-independent features of the B-cell compartment in SLE are less understood.In this study,we performed an extensive examination of B-cell subsets and their proinflammatory properties in a Chinese cohort of new-onset SLE patients.We observed that SLE patients exhibited an increased frequency of transitional B cells compared with healthy donors and rheumatoid arthritis patients.Plasma from SLE patients potently promoted the survival of transitional B cells in a type I IFN-dependent manner,which can be recapitulated by direct IFN-αtreatment.Furthermore,the effect of IFN-αon enhanced survival of transitional B cells was associated with NF-κB pathway activation and reduced expression of the pro-apoptotic molecule Bax.Transitional B cells from SLE patients harbored a higher capacity to produce proinflammatory cytokine IL-6,which was also linked to the overactivated type I IFN pathway.In addition,the frequency of IL-6-producing transitional B cells was positively correlated with disease activity in SLE patients,and these cells were significantly reduced after short-term standard therapies.Thus,the current study provides a direct link between type I IFN pathway overactivation and the abnormally high frequency and proinflammatory properties of transitional B cells in active SLE patients,which contributes to the understanding of the roles of type I IFNs and B cells in the pathogenesis of SLE.
