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| 1 | IL-10-producing regulatory B cells restrain the T follicular helper cell response in primary Sjögren’s syndrome显示文摘Increased numbers of T follicular helper(Tfh)cells have been implicated in the development of autoimmune diseases including primary Sjögren’s syndrome(pSS),but how the Tfh cell response is regulated during autoimmune pathogenesis remains largely unclear.Here,we first found negative correlations between IL-10^(+)regulatory B(Breg)cell numbers and Tfh cell responses and disease activity in patients with pSS and mice with experimental Sjögren’s syndrome(ESS).Moreover,we detected high expression of IL-10 receptor on Tfh cells and their precursors in both humans and mice.In culture,IL-10 suppressed human and murine Tfh cell differentiation by promoting STAT5 phosphorylation.By using an adoptive transfer approach and two-photon live imaging,we found significantly increased numbers of Tfh cells with enhanced T cell homing into B cell follicles in the draining cervical lymph nodes of RAG-2−/−mice transferred with IL-10-deficient B cells during ESS development compared with those of RAG-2−/−mice transferred with wild-type B cells.In ESS mice,CD19^(+)CD1d^(hi)CD5^(+)Breg cells with decreased IL-10 production exhibited severely impaired suppressive effects on T cell proliferation.Consistently,CD19^(+)CD24^(+)CD38^(hi) Breg cells from pSS patients showed significantly reduced IL-10 production with defective inhibitory function in the suppression of autologous Tfh cell expansion.Furthermore,the adoptive transfer of IL-10-producing Breg cells markedly suppressed the Tfh cell response and ameliorated ESS progression in ESS mice.Together,these findings demonstrate a critical role for IL-10-producing Breg cells in restraining the effector Tfh cell response during pSS development. | Xiang Lin Xiaohui Wang Fan Xiao Kongyang Ma Lixiong Liu Xiaoqi Wang Dong Xu Fei Wang Xiaofei Shi Dongzhou Liu Yan Zhao Liwei Lu | 2019 | Cellular & Molecular Immunology2019，16，12： | 13 |
| 2 | Epigenetic regulation in B-cell maturation and its dysregulation in autoimmunity显示文摘B cells have a critical role in the initiation and acceleration of autoimmune diseases, especially those mediated byautoantibodies. In the peripheral lymphoid system, mature B cells are activated by self or/and foreign antigens andsignals from helper T cells for differentiating into either memory B cells or antibody-producing plasma cells.Accumulating evidence has shown that epigenetic regulations modulate somatic hypermutation and class switchDNA recombination during B-cell activation and differentiation. Any abnormalities in these complex regulatoryprocesses may contribute to aberrant antibody production, resulting in autoimmune pathogenesis such as systemiclupus erythematosus. Newly generated knowledge from advanced modern technologies such as next-generationsequencing, single-cell sequencing and DNA methylation sequencing has enabled us to better understand B-cellbiology and its role in autoimmune development. Thus this review aims to summarize current research progress inepigenetic modifications contributing to B-cell activation and differentiation, especially under autoimmuneconditions such as lupus, rheumatoid arthritis and type 1 diabetes. | Haijing Wu Yaxiong Deng Yu Feng Di Long Kongyang Ma Xiaohui Wang Ming Zhao Liwei Lu Qianjin Lu | 2018 | Cellular & Molecular Immunology2018，15，7： | 10 |
| 3 | IL-17 sustains the plasma cell response via p38-mediated Bcl-xL RNA stability in lupus pathogenesis显示文摘Recent studies have demonstrated a central role for plasma cells in the development of autoimmune diseases,such as systemic lupus erythematosus(SLE).Currently,both the phenotypic features and functional regulation of autoreactive plasma cells during SLE pathogenesis remain largely unclear.In this study,we first found that a major subset of IL-17 receptor-expressing plasma cells potently produced anti-dsDNA IgG upon IL-17A(IL-17)stimulation in SLE patients and lupus mice.Using a humanized lupus mouse model,we showed that the transfer of Th17 cell-depleted PBMCs from lupus patients resulted in a significantly reduced plasma cell response and attenuated renal damage in recipient mice compared to the transfer of total SLE PBMCs.Moreover,long-term BrdU incorporation in lupus mice detected highly enriched long-lived BrdU+subsets among IL-17 receptor-expressing plasma cells.Lupus mice deficient in IL-17 or IL-17 receptor C(IL-17RC)exhibited a diminished plasma cell response and reduced autoantibody production with attenuated renal damage,while the adoptive transfer of Th17 cells triggered the plasma cell response and renal damage in IL-17-deficient lupus mice.In reconstituted chimeric mice,IL-17RC deficiency resulted in severely impaired plasma cell generation but showed no obvious effect on germinal center B cells.Further mechanistic studies revealed that IL-17 significantly promoted plasma cell survival via p38-mediated Bcl-xL transcript stabilization.Together,our findings identified a novel function of IL-17 in enhancing plasma cell survival for autoantibody production in lupus pathogenesis,which may provide new therapeutic strategies for the treatment of SLE. | Kongyang Ma Wenhan Du Fan Xiao Man Han Enyu Huang Na Peng Yuan Tang Chong Deng Lixiong Liu Yulan Chen Jingjing Li Shiwen Yuan Qin Huang Xiaoping Hong Dajun Hu Xiaoyan Cai Quan Jiang Dongzhou Liu Liwei Lu | 2021 | Cellular & Molecular Immunology2021，18，7： | 6 |
| 4 | The expanding functional diversity of plasma cells in immunity and inflammation显示文摘The generation and function of plasma cells have been well recognized as the central events in humoral immunity.In particular,long-lived plasma cells,characterized by a long lifespan and the lack of cell division,persistently secrete high-affinity antibodies to maintain serum antibody titers in the immune response and autoimmune inflammation.Although the significant expansion of plasma cells is observed during the aging process,autoimmune diseases and chronic infections,the expanding functional diversity and underlying mechanisms of plasma cells remain incompletely understood.Here,we describe recent advances in revealing new functional subsets and phenotypic features of plasma cells in aging and autoimmunity. | Kongyang Ma Xiaohui Wang Xiaofei Shi Xiang Lin Fan Xiao Xin Ma Dongzhou Liu Liwei Lu | 2020 | Cellular & Molecular Immunology2020，17，4： | 2 |
| 5 | New insights into the significance of the BCR repertoire in B-1 cell development and function显示文摘As an important player of innate immunity,B-1 cells have been characterized by natural antibody production and rapid immune response.Based on their expression or lack of CD5,B-1 cells are further separated into B-1a and B-1b subsets.1 Although extensive studies have demonstrated a pivotal role of conventional B cells in adaptive immunity,there is increasing evidence indicating the close associations of B-1a cells with self-reactivity,autoimmunity,infection,and even leukemia.2–4 Here,we describe recent advances that lead to a clearer understanding of B-1 cell development with a focus on new insights into the significance of the B-cell receptor(BCR)repertoire in B-1a cell biology and discuss the potential strategies for specific targeting of B-1a cells under pathological settings. | Xiaohui Wang Cong Ye Xiang Lin Kongyang Ma Fan Xiao Lingli Dong Liwei Lu | 2019 | Cellular & Molecular Immunology2019，16，9： | 2 |
| 6 | B1-cell-produced anti-phosphatidylserine antibodies contribute to lupus nephritis development via TLR-mediated Syk activation显示文摘Autoantibodies produced by B cells play a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE). However, both the cellular source of antiphospholipid antibodies and their contributions to the development of lupus nephritis (LN) remain largely unclear. Here, we report a pathogenic role of anti-phosphatidylserine (PS) autoantibodies in the development of LN. Elevated serum PS-specific IgG levels were measured in model mice and SLE patients, especially in those with LN. PS-specific IgG accumulation was found in the kidney biopsies of LN patients. Both transfer of SLE PS-specific IgG and PS immunization triggered lupus-like glomerular immune complex deposition in recipient mice. ELISPOT analysis identified B1a cells as the main cell type that secretes PS-specific IgG in both lupus model mice and patients. Adoptive transfer of PS-specific B1a cells accelerated the PS-specific autoimmune response and renal damage in recipient lupus model mice, whereas depletion of B1a cells attenuated lupus progression. In culture, PS-specific B1a cells were significantly expanded upon treatment with chromatin components, while blockade of TLR signal cascades by DNase I digestion and inhibitory ODN 2088 or R406 treatment profoundly abrogated chromatin-induced PS-specific IgG secretion by lupus B1a cells. Thus, our study has demonstrated that the anti-PS autoantibodies produced by B1 cells contribute to lupus nephritis development. Our findings that blockade of the TLR/Syk signaling cascade inhibits PS-specific B1-cell expansion provide new insights into lupus pathogenesis and may facilitate the development of novel therapeutic targets for the treatment of LN in SLE. | Kongyang Ma Wenhan Du Shiyun Wang Fan Xiao Jingyi Li Jie Tian Yida Xing Xiaodan Kong Ke Rui Rencai Qin Xiaoxia Zhu Jing Wang Cainan Luo Haijing Wu Yun Zhang Chengping Wen Lan He Dongzhou Liu Hejian Zou Qianjin Lu Lijun Wu Liwei Lu | 2023 | Cellular & Molecular Immunology2023，20，8： | 0 |
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