Xing Chen, Zhu Gaizhi, Xiao He, Fang Ying, Liu Xiaoling, Han Gencheng, Chen Guojiang, Hou Chunmei, Shen Beifen, Li Yan, Ma Ning, Wang Renxi
Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
Department of Stress Medicine, Beijing Institute of Basic Medical Sciences, Beijing, China.
Oncotarget. 2017 Jul 5;8(52):89486-89499. doi: 10.18632/oncotarget.19002. eCollection 2017 Oct 27.
Previous studies have shown that under normal physiological conditions thymic B cells play a critical function in T cell negative selection. We tested the effect of thymic B cells on thymic T-cell differentiation in autoimmune diseases including systemic lupus erythematosus (SLE). We found that thymic B cells and CD8 CD4 and CD4CD8T cells increased, whereas CD4CD8T cells decreased in lupus-prone mice. Once B cells were reduced, the change was reversed. Furthermore, we found that B cells blocked thymic immature single positive (ISP) CD4CD8CD3RORγt T cells progression into CD4CD8T cells. Interestingly, we found a novel population of thymic immature T cells (CD4CD8CD3RORγt) that were induced into mature CD4CD8CD3RORγtT cells by B cells in lupus-prone mice. Importantly, we found that IgG, produced by thymic B cells, played a critical role in the differentiation of thymic CD8ISP and mature RORγtCD8 T cells in lupus-prone mice. In conclusion, B cells blocked the differentiation from thymic CD8ISP and induced the differentiation of a novel immature CD4CD8CD3RORγtT cells into mature RORγtCD8 T cells by secreting IgG antibody in lupus-prone mice.
先前的研究表明，在正常生理条件下，胸腺B细胞在T细胞阴性选择中发挥关键作用。我们测试了胸腺B细胞对包括系统性红斑狼疮（SLE）在内的自身免疫性疾病中胸腺T细胞分化的影响。我们发现，在易患狼疮的小鼠中，胸腺B细胞以及CD8 CD4和CD4CD8 T细胞增加，而CD4CD8 T细胞减少。一旦B细胞减少，这种变化就会逆转。此外，我们发现B细胞阻断了胸腺未成熟单阳性（ISP）CD4CD8CD3RORγt T细胞向CD4CD8 T细胞的进展。有趣的是，我们发现了一种新的胸腺未成熟T细胞群体（CD4CD8CD3RORγt），在易患狼疮的小鼠中，它们被B细胞诱导成为成熟的CD4CD8CD3RORγt T细胞。重要的是，我们发现胸腺B细胞产生的IgG在易患狼疮的小鼠胸腺CD8 ISP和成熟RORγt CD8 T细胞的分化中起关键作用。总之，在易患狼疮的小鼠中，B细胞通过分泌IgG抗体阻断胸腺CD8 ISP的分化，并诱导新的未成熟CD4CD8CD3RORγt T细胞分化为成熟的RORγt CD8 T细胞。
