Ma Ning, Zhang Yu, Liu Qilin, Wang Zhiding, Liu Xiaoling, Zhu Gaizhi, Yu Dandan, Han Gencheng, Chen Guojiang, Hou Chunmei, Wang Tianxiao, Ma Yuanfang, Shen Beifen, Li Yan, Xiao He, Wang Renxi
Department of Rheumatology, First hospital of Jilin University, Changchun 130021, China.
Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China; College of Pharmacy, Henan University, Kaifeng 475004, China.
Mol Immunol. 2017 May;85:18-26. doi: 10.1016/j.molimm.2017.02.002. Epub 2017 Feb 12.
B cell activating factor (BAFF) regulates B cell maturation, survival, function, and plays a critical pathogenic role in autoimmune diseases. It remains unclear how BAFF affects IL-10B cells versus regulatory B cells (Bregs) in inflammatory responses. In this study, we found that IL-10-expressing Bregs decreased in lupus-prone MRL/lpr mice and experimental allergic encephalomyelitis (EAE) mice. On blockade of the effects of BAFF with TACI-IgG, IL-10 Bregs were upregulated in MRL/lpr and EAE mice. In addition, BAFF expanded IL-10B cells over IL-10B cells under noninflammatory conditions in vitro, whereas it expanded IL-10B cells over IL-10B cells during inflammatory responses, such as stimulation with autoantigen and LPS. Finally, the selection of IL-10B cells over IL-10B cells by BAFF was dependent on BAFF receptors (BAFFR, TACI, and BCMA) that were upregulated by inflammatory responses. This study suggests that BAFF selects IL-10B cells over IL-10 regulatory B cells via BAFF receptors in inflammatory responses.
B细胞活化因子（BAFF）调节B细胞的成熟、存活和功能，并在自身免疫性疾病中发挥关键的致病作用。目前尚不清楚BAFF在炎症反应中如何影响分泌白细胞介素10的B细胞（IL-10B细胞）与调节性B细胞（Bregs）。在本研究中，我们发现，在易患狼疮的MRL/lpr小鼠和实验性自身免疫性脑脊髓炎（EAE）小鼠中，表达IL-10的Bregs数量减少。用TACI-IgG阻断BAFF的作用后，MRL/lpr和EAE小鼠中的IL-10 Bregs上调。此外，在体外非炎症条件下，BAFF使IL-10B细胞相对于IL-10调节性B细胞扩增，而在炎症反应期间，如用自身抗原和脂多糖刺激时，BAFF使IL-10调节性B细胞相对于IL-10B细胞扩增。最后，BAFF对IL-10调节性B细胞与IL-10B细胞的选择取决于炎症反应上调的BAFF受体（BAFFR、TACI和BCMA）。本研究表明，在炎症反应中，BAFF通过BAFF受体选择IL-10B细胞而非IL-10调节性B细胞。
