A role for CMTM7 in BCR expression and survival in B-1a but not B-2 cells.

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.