Involvement of Zizimin2/3 in the age-related defect of peritoneal B-1a cells as a source of anti-bacterial IgM

International Immunology
Akihiko SakamotoMitsuo Maruyama

Abstract

Zizimin2 (Ziz2), also known as dedicator of cytokinesis 11 (DOCK11), is a guanine nucleotide exchange factor that is predominantly expressed in lymphoid tissues. Recent findings demonstrated that Ziz2 is involved in the development of B cells, including germinal centre B cells and marginal zone B cells. However, limited information is currently available on the roles of Ziz2 in B-1 cells, a B-cell subset that resides in body cavities and contributes to protection against foreign pathogens in a T-cell-independent manner. We herein show that Ziz2 and its widely expressed isoform Ziz3 (also known as DOCK10) may be involved in defective production of anti-bacterial IgM by aged B-1a cells, a CD5+ subset of B-1 cells. Natural IgM against typical bacterial epitopes was defectively produced by peritoneal B-1a cells from aged mice. The down-regulation of Ziz2/3 in B-1a cells appeared to be responsible for this defective IgM production, as demonstrated by Ziz2/3 double-knockout mice. Mechanistically, lower levels of basal AKT phosphorylation did not allow for the differentiation of Ziz2/3-deficient B-1a cells into plasma cells. Defective production of anti-bacterial IgM was not fully rescued by immunization, resulting in slightly weaker ...Continue Reading

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Citations

Mar 3, 2020·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Mitsuo MaruyamaAkinori Takaoka
Apr 4, 2020·The Journal of Biological Chemistry·Kazuhiko NamekataTakayuki Harada
Mar 9, 2021·The Journal of Biological Chemistry·Andrew P ThompsonPaul E Brennan

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