CMTM7 plays key roles in TLR‐induced plasma cell differentiation and p38 activation in murine B‐1 B cells. Issue 6 (18th February 2020)

• Record Type: Journal Article
• Authors: Liu, Zhengyang; Liu, Yuan; Li, Ting; Wang, Pingzhang; Mo, Xiaoning; Lv, Ping; Ma, Dalong; Han, Wenling
• Is Part Of: European journal of immunology. Volume 50:Issue 6(2020)
• Page Start: 809
• Page End: 821
• Publication Date: 2020-02-18
• Subjects: B‐1 cells -- CMTM7 -- IgM -- IL‐10 -- p38 signaling -- plasma cells; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201948363
• Languages: English
• ISSNs: 0014-2980

Abstract

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. Abstract : Ligation of TLRs activates the NF‐κB pathway and MAPK cascades, including ERK, JNK, and p38. Among these molecules, p38 signaling acts as a key regulator that modulates the expression of plasma cell differentiation transcription factors. In Cmtm7 ‐deficient B‐1 cells, the decreased phospho‐p38 levels contribute to impaired plasma cell differentiation.