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

Abstract

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.