| First Author | Sakamoto A | Year | 2017 |
| Journal | Int Immunol | Volume | 29 |
| Issue | 9 | Pages | 431-438 |
| PubMed ID | 29099971 | Mgi Jnum | J:271416 |
| Mgi Id | MGI:5921660 | Doi | 10.1093/intimm/dxx054 |
| Citation | Sakamoto A, et al. (2017) Involvement of Zizimin2/3 in the age-related defect of peritoneal B-1a cells as a source of anti-bacterial IgM. Int Immunol 29(9):431-438 |
| abstractText | 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 protection in Ziz2/3-deficient mice. Thus, the down-regulation of Ziz2/3 in B-1a cells may at least partly account for defective protection in aged mice. |
