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

Int Immunol. 2017 Nov 1;29(9):431-438. doi: 10.1093/intimm/dxx054.


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.

Keywords: DOCK10/11; peritoneal cavity; systemic infection; type 3 Streptococcus pneumoniae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology*
  • Animals
  • Antibodies, Bacterial / metabolism
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocytes / immunology*
  • CD5 Antigens / metabolism
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Guanine Nucleotide Exchange Factors / genetics*
  • Guanine Nucleotide Exchange Factors / metabolism
  • Immunoglobulin M / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peritoneal Cavity / cytology


  • Antibodies, Bacterial
  • CD5 Antigens
  • DOCK10 protein, mouse
  • Dock11 protein, mouse
  • Guanine Nucleotide Exchange Factors
  • Immunoglobulin M