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Essential role for Cmtm7 in cell-surface phenotype, BCR signaling, survival and Ig mu repertoire of splenic B-1a cells

机译:CMTM7在细胞表面表型中的基本作用,BCR信号,存活和IGU曲线的脾β1a细胞

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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.
机译:B-1A细胞代表具有独特的表型,自更新能力和限制Ig Mu Reptoire的不同B细胞群。它们主要位于体腔中,也存在于脾脏中。 B-1A细胞的不同亚群受到当地环境的严重影响。我们以前的研究表明,含味道域的膜蛋白CMTM7参与B-1A细胞发育。在这里,我们将其对腹膜和脾脏B-1a细胞的影响。与腹膜B-1A细胞不同,我们发现脾脏CMTM7( - / - )B-1A细胞与WT对应物相比表达了更高水平的CD5,CD80和CD86。它们还在稳定状态下表现出增强的补品BCR信号。虽然细胞活力在体外不受影响,但CMTM7敲除明显促进脾脏B-1A细胞凋亡,其可能与IL-5Rα的下调有关。关于IGU EREPEROIRE,腹膜和脾脏CMTM7( - / - )B-1A细胞表现出类似于V(H)11的损失和V(H)12的增益的类似变化,而V(H)增加从j(h)1到j(h)2和j(h)4个系列中只能在脾cmtm7( - / - )b-1a细胞内检测到来自j(h)1到j(h)的偏孔的j段。总体而言,这些数据表明CMTM7在腹膜和脾脏B-1A细胞中以不同的作用,并在脾细胞中起更重要的作用。

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