A role for CMTM7 in BCR expression and survival in B-1a but not B-2 cells.
A role for CMTM7 in BCR expression and survival in B-1a but not B-2 cells.
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DOI：
10.1093/intimm/dxt042
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发表时间：
2014
影响因子：
4.4
通讯作者：
Yanfei Zhang;Ji-Yang Wang;W. Han
中科院分区：
文献类型：
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作者：
Yanfei Zhang;Ji-Yang Wang;W. Han
B-1细胞是产生天然抗体和前线宿主防御的重要细胞群。在这里，我们发现含有漫威结构域的膜蛋白CMTM7 （CKLF-like MARVEL跨膜结构域7）在B-1a细胞的BCR表达和存活中起关键作用。我们分析了用Cmtm7（flox/⁺）胎儿肝细胞重组的Rag1毒血症/毒血症的淋巴细胞发育情况，因为Cmtm7（flox/⁺）杂合子具有意想不到的致命性。我们发现用Cmtm7（flox/⁺）细胞重组的Rag1⁻/⁻小鼠与野生型（WT）细胞重组的小鼠相比，血清IgM和腹膜中B-1a的数量有轻微的减少。Cmtm7（flox/⁺）小鼠中B-1a细胞的减少与这些细胞中BCR表达的降低和自发细胞死亡的增加有关。此外，来自Cmtm7（flox/⁺）胎肝细胞的B-1a和B-1b细胞中，能够自发分化为分泌igm的浆细胞的细胞频率低于来自WT胎肝细胞的细胞。此外，Cmtm7（flox/⁺）B-1a和B-1b细胞对lps诱导的增殖反应较差。与B-1细胞的缺陷形成鲜明对比的是，Cmtm7（flox/⁺）B-2细胞与WT B-2细胞相比没有表现出明显的异常。这些结果证明了CMTM7在B-1a细胞BCR表达和存活中的特殊作用。
B-1 cells are an important cell population for the production of natural antibodies and front-line host defense. Here, we show that the MARVEL-domain-containing membrane protein CMTM7 (CKLF-like MARVEL transmembrane domain-containing 7) plays a critical role in BCR expression and survival in B-1a cells. We analyzed lymphocyte development in Rag1⁻/⁻ mice reconstituted with Cmtm7(flox/⁺) fetal liver cells because of the unexpected lethality of the Cmtm7(flox/⁺) heterozygotes. We found a mild reduction of serum IgM and a significantly reduced B-1a population in the peritoneal cavity of Rag1⁻/⁻ mice reconstituted with Cmtm7(flox/⁺) cells compared with those reconstituted with wild-type (WT) cells. The reduction of B-1a cells in Cmtm7(flox/⁺) mice was associated with reduced BCR expression and increased spontaneous cell death in these cells. In addition, both B-1a and B-1b cells derived from Cmtm7(flox/⁺) fetal liver cells contained a lower frequency of cells capable of spontaneously differentiating into IgM-secreting plasma cells than did those derived from WT fetal liver cells. Furthermore, Cmtm7(flox/⁺) B-1a and B-1b cells responded poorly to LPS-induced proliferation. In striking contrast to the defects in B-1 cells, Cmtm7(flox/⁺) B-2 cells did not show obvious abnormalities when compared with WT B-2 cells. These results demonstrate a specific role for CMTM7 in BCR expression and survival in B-1a cells.