Cmtm7 knockout inhibits B-1a cell development at the transitional (TrB-1a) stage
Cmtm7 knockout inhibits B-1a cell development at the transitional (TrB-1a) stage
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Cmtm7 敲除抑制过渡 (TrB-1a) 阶段的 B-1a 细胞发育
DOI：
10.1093/intimm/dxz041
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发表时间：
2019
影响因子：
4.4
通讯作者：
Wenling Han
中科院分区：
文献类型：
--
作者：
Zhengyang Liu;Yuan Liu;Ting Li;Pingzhang Wang;Xiaoning Mo;Ping Lv;Qing Ge;Dalong Ma;Wenling Han
天然样B-1a细胞是产生天然IgM和白细胞介素-10（IL-10）的重要细胞群，并且充当抵抗病原体的第一线。我们确定CMTM 7对于B-1a细胞发育是必需的。在Cmtm 7（CKLF样MARVEL跨膜结构域7）敲除后，所有研究组织中的B-1a细胞数量均显著减少。利用骨髓和胎肝过继转移模型和条件性基因敲除小鼠，我们发现B-1a细胞的减少是由B细胞内在缺陷引起的。由于B-1a细胞丢失，Cmtm 7缺陷小鼠产生更少的IgM和IL-10，并且更容易受到微生物败血症的影响。Cmtm 7 −/−小鼠成熟B-1a细胞的自我更新和稳态没有受损，表明Cmtm 7对B-1a细胞发育的影响。进一步研究表明，Cmtm 7在B-1a细胞发育中的作用发生在特定的过渡期B-1a（TrB-1a），Cmtm 7缺陷导致TrB-1a细胞增殖缓慢，细胞死亡率高。因此，Cmtm 7在过渡期控制B-1a细胞的发育。
Innate-like B-1a cells are an important cell population for production of natural IgM and interleukin-10 (IL-10), and act as the first line against pathogens. We determined that CMTM7 is essential for B-1a cell development. Following Cmtm7 (CKLF-like MARVEL transmembrane domain-containing 7) knockout, B-1a cell numbers decreased markedly in all investigated tissues. Using a bone marrow and fetal liver adoptive transfer model and conditional knockout mice, we showed that the reduction of B-1a cells resulted from B-cell-intrinsic defects. Because of B-1a cell loss,Cmtm7-deficient mice produced less IgM and IL-10, and were more susceptible to microbial sepsis. Self-renewal and homeostasis of mature B-1a cells inCmtm7−/−mice were not impaired, suggesting the effect ofCmtm7on B-1a cell development. Further investigations demonstrated that the function ofCmtm7in B-1a cell development occurred at the specific transitional B-1a (TrB-1a) stage.Cmtm7deficiency resulted in a slow proliferation and high cell death rate of TrB-1a cells. Thus,Cmtm7controls B-1a cell development at the transitional stage.