Essential role for Cmtm7 in cell-surface phenotype, BCR signaling, survival and Igμ repertoire of splenic B-1a cells
Essential role for Cmtm7 in cell-surface phenotype, BCR signaling, survival and Igμ repertoire of splenic B-1a cells
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DOI：
10.1016/j.cellimm.2020.104100
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发表时间：
2020-06-01
影响因子：
4.3
通讯作者：
Han, Wenling
中科院分区：
文献类型：
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作者：
Liu, Zhengyang;Liu, Yuan;Han, Wenling
B-1a细胞是一种独特的B细胞群，具有独特的表型、自我更新能力和有限的IG mu库。它们主要分布于体腔，也存在于脾脏。B-1a细胞的不同亚群受到局部环境的严重影响。我们的前期研究表明，含MARVEL结构域的膜蛋白CMTM 7参与了B-1a细胞的发育。在这里，我们集中其对腹膜和脾B-1a细胞的影响。与腹膜B-1a细胞不同，我们发现脾脏Cmtm 7（-/-）B-1a细胞与WT细胞相比表达更高水平的CD 5、CD 80和CD 86。它们在稳态下也表现出增强的强直性BCR信号。Cmtm 7基因敲除可显著促进脾B-1a细胞原位凋亡，这可能与IL-5 r α表达下调有关。关于IG mu库，腹膜和脾Cmtm 7（-/-）B-1a细胞表现出类似的变化，例如V（H）11的丢失和V（H）12的增加，而V（H）1使用的增加和从J（H）1到J（H）2和J（H）4家族的偏斜J片段只能在脾Cmtm 7（-/-）B-1a细胞中检测到。总之，这些数据表明Cmtm 7在腹膜和脾B-1a细胞中的功能不同，并且在脾细胞中起更重要的作用。
B-1a cells represent a distinct B cell population with unique phenotype, self-renewing capacity and restricted Ig mu repertoire. They primarily locate in body cavity and also exist in spleen. The different subpopulations of B-1a cells are heavily affected by local environment. Our previous studies revealed that MARVEL-domain-containing membrane protein, CMTM7, was involved in B-1a cell development. Here, we focused its influence on peritoneal and splenic B-1a cells. Unlike peritoneal B-1a cells, we found that splenic Cmtm7(-/-) B-1a cells expressed higher level of CD5, CD80 and CD86 compared with WT counterparts. They also exhibited an enhanced tonic BCR signals in steady state. Though the cell viability was unaffected in vitro, Cmtm7 knockout markedly promoted splenic B-1a cell apoptosis in situ, which was likely associated with down-regulation of Il-5r alpha. With regard to Ig mu repertoire, peritoneal and splenic Cmtm7(-/-) B-1a cells exhibit similar changes exemplified by the loss of V(H)11 and gain of V(H)12, whereas an increase in V(H)1 usage and skewed J segments from J(H)1 to J(H)2 and J(H)4 families could only be detected within splenic Cmtm7(-/-) B-1a cells. Overall, these data indicate that Cmtm7 functions differently in peritoneal and splenic B-1a cells and plays a more important role in splenic cells.