CMTM7 plays key roles in TLR‐induced plasma cell differentiation and p38 activation in murine B‐1 B cells
Open Access
- 5 February 2020
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 50 (6), 809-821
- https://doi.org/10.1002/eji.201948363
Abstract
Terminal differentiation of B cells into antibody-secreting cells is the foundation of humoral immune response. B-1 cells, which are different from B-2 cells, preferentially differentiate into plasma cells. CMTM7 is a MARVEL-domain-containing membrane protein predominantly expressed in B cells that plays an important role in B-1a cell development. The present study assessed CMTM7 function in response to antigen stimulation. Following immunization with T cell-dependent and T cell-independent antigens, Cmtm7-deficient mice exhibited decreased IgM but normal IgG responses in vivo. In vitro stimulation with LPSs induced Cmtm7−/− B-1 cell activation, whereas proliferation was marginally reduced. Notably, Cmtm7 deficiency markedly suppressed plasma cell differentiation in response to TLR agonists, accompanied by a decrease in IgM and IL-10 production. At the molecular level, loss of Cmtm7 repressed the downregulation of Pax5 and the upregulation of Xbp1, Irf4, and Prdm1. Furthermore, p38 phosphorylation was inhibited in Cmtm7−/− B-1 cells. Experiments using a p38 inhibitor revealed that p38 activation was essential for the terminal differentiation of B-1 cells, suggesting that Cmtm7 contributes to B-1 cell differentiation by maintaining p38 activation. Overall, the data reveal the crucial functions of CMTM7 in TLR-induced terminal differentiation and p38 activation in B-1 cells.Keywords
Funding Information
- National Natural Science Foundation of China (81771680, 81273207)
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