The immunosenescence-related factor DOCK11 is involved in secondary immune responses of B cells

Abstract

Background Memory B cells are an antigen-experienced B-cell population with the ability to rapidly differentiate into antibody-producing cells by recall responses. We recently found that dedicator of cytokinesis 11 (DOCK11) contributes to the expansion of antigen-specific populations among germinal center B cells upon immunization. In comparison, limited information is available on the contribution of DOCK11 to secondary humoral immune responses. Results In this study, effects of the DOCK11 deficiency in B cells were examined on secondary immune responses to protein antigen. The lack of DOCK11 in B cells resulted in the impaired induction of antibody-producing cells upon secondary immunization with protein antigen. DOCK11 was dispensable for the recall responses of antigen-experienced B cells, as demonstrated by the comparable induction of antibody-producing cells in mice given transfer of antigen-experienced B cells with no DOCK11 expression. Instead, the lack of DOCK11 in B cells resulted in the impaired secondary immune responses in a B cell-extrinsic manner, which was recovered by the adoptive transfer of cognate T cells. Conclusions We addressed that intrinsic and extrinsic effects of DOCK11 expression in B cells may contribute to secondary humoral immune responses in manner of the induction of cognate T-cell help.

Markers of immune dysregulation in response to the ageing gut: insights from aged murine gut microbiota transplants

“…Specifically, CXCL9 has been associated with regenerated islet-derived protein-mediated microbiota expression, which when under-expressed is suggested to be responsible for lower microbial diversity [ 37 ]. Moreover, DOCK11, a mediator of cytokinesis, is another contributor of immunosenescence during ageing, although independent of B cell antibody responses [ 38 ]. For instance, mice with DOCK11-deificient B cells have reduced antigen-specific participation in germinal centers, which is accompanied by lower B cell intrinsic-signaling stimulation [ 39 ].…”

Roles Played by DOCK11, a Guanine Nucleotide Exchange Factor, in HBV Entry and Persistence in Hepatocytes

“…In mouse lymphoid tissue, both the Fcγ (Fc gamma) receptor and TLR4 (toll-like receptor 4) have been shown to upregulate and stabilize DOCK11 expression, thereby promoting filopodial formation via CDC42 activation in bone marrow-derived dendritic cells, indicating that DOCK11 plays a role in immune system modulation [27]. In addition, because the expression of DOCK11 is regulated by age-dependent mechanisms, any age-associated downregulation of DOCK11 in B cells could impact secondary immune responses [28]. Furthermore, DOCK11 mRNA and protein expressions exhibit good correspondence [29], suggesting that regulation of DOCK11 expression could be relatively straightforward.…”