CMTM7 plays key roles in TLR-induced plasma cell differentiation and p38 activation in murine B-1 B cells.,European Journal of Immunology

当前位置： X-MOL 学术 › Eur. J. Immunol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

CMTM7 plays key roles in TLR-induced plasma cell differentiation and p38 activation in murine B-1 B cells.
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-02-05 , DOI: 10.1002/eji.201948363
Zhengyang Liu _{1,

2} , Yuan Liu _{1,

2} , Ting Li _{1,

2} , Pingzhang Wang _{1,

2} , Xiaoning Mo _{1,

2} , Ping Lv _{1,

2} , Dalong Ma _{1,

2} , Wenling Han _{1,

2}

Affiliation

Terminal differentiation of B cells into antibody‐secreting cells is the foundation of humoral immune response. B‐1 cells, which are different from B‐2 cells, preferentially differentiate into plasma cells. CMTM7 is a MARVEL‐domain‐containing membrane protein predominantly expressed in B cells that plays an important role in B‐1a cell development. The present study assessed CMTM7 function in response to antigen stimulation. Following immunization with T cell‐dependent and T cell‐independent antigens, Cmtm7 ‐deficient mice exhibited decreased IgM but normal IgG responses in vivo. In vitro stimulation with LPSs induced Cmtm7^−/− B‐1 cell activation, whereas proliferation was marginally reduced. Notably, Cmtm7 deficiency markedly suppressed plasma cell differentiation in response to TLR agonists, accompanied by a decrease in IgM and IL‐10 production. At the molecular level, loss of Cmtm7 repressed the downregulation of Pax5 and the upregulation of Xbp1 , Irf4 , and Prdm1 . Furthermore, p38 phosphorylation was inhibited in Cmtm7^−/− B‐1 cells. Experiments using a p38 inhibitor revealed that p38 activation was essential for the terminal differentiation of B‐1 cells, suggesting that Cmtm7 contributes to B‐1 cell differentiation by maintaining p38 activation. Overall, the data reveal the crucial functions of CMTM7 in TLR‐induced terminal differentiation and p38 activation in B‐1 cells.

中文翻译：

CMTM7在鼠B-1 B细胞中TLR诱导的浆细胞分化和p38激活中起关键作用。

B细胞最终分化为分泌抗体的细胞是体液免疫反应的基础。与B-2细胞不同的B-1细胞优先分化为浆细胞。CMTM7是含MARVEL结构域的膜蛋白，主要在B细胞中表达，在B-1a细胞发育中起重要作用。本研究评估了响应抗原刺激的CMTM7功能。用依赖T细胞和不依赖T细胞的抗原免疫后，Cmtm7缺陷小鼠体内的IgM降低，但IgG反应正常。LPS的体外刺激诱导Cmtm7 ^-/- B-1细胞活化，而增殖则略有降低。值得注意的是，Cmtm7缺乏显着抑制了响应TLR激动剂的浆细胞分化，并伴有IgM和IL-10产生的减少。在分子水平上，损失Cmtm7压抑的下调PAX5和上调XBP1，IRF4和PRDM1。此外，p38磷酸化在Cmtm7 ^-/- B-1细胞中受到抑制。使用p38抑制剂的实验表明，p38激活对于B-1细胞的终末分化至关重要，这表明Cmtm7通过维持p38活化来促进B-1细胞分化。总体而言，数据揭示了CMTM7在TLR诱导的B-1细胞终末分化和p38激活中的关键功能。

更新日期：2020-02-05

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11