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.
Peking University Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China.
Yanfei
Y
Zhang
Ji-Yang
JY
Wang
Wenling
W
Han
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D049109:Cell Proliferation; D018925:Chemokines; D018398:Homeodomain Proteins / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D062792:MARVEL Domain-Containing Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL
C573093:CMTM7 protein, mouse; D018925:Chemokines; D018398:Homeodomain Proteins; D007075:Immunoglobulin M; D062792:MARVEL Domain-Containing Proteins; D008565:Membrane Proteins; C064658:RAG-1 protein
B-1a; BCR expression; CMTM7; cell death; natural IgM