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.

Background: An atypical B cell subset of age-associated B cells (ABCs) accumulate with age in mice and humans. ABCs acquire the ability to secrete antibodies and inflammatory cytokines in response to TLR7 and TLR9, and present antigens to T cells more efficiently than follicular (FO) B cells, which promotes the development of pathogenic phenotypes in aged individuals. Results:In this study, we demonstrated that actin cytoskeleton remodeling is enhanced in ABCs compared to FO B cells. ABCs showed higher motility across Transwell membranes and 3-dimensional (3D) collagen gels, without chemoattractants. Due to chemokine receptor expression remodeling, ABCs were attracted by CXCL12 and CCL21 rather than CXCL13. Among F-actin remodeling-related factors, expression levels of Fascin1 and Pak1 were increased in ABCs. In the presence of a Pak1 inhibitor, IPA3, migration of ABCs in both Transwell chambers and 3D-collagen gels was significantly attenuated. In contrast, a Fascin1 inhibitor, migrastatin, only reduced ABC migration in the 3D collagen gel. The ability to present antigens to T cells was also enhanced in ABCs, in which the Fascin1 mediated pathway is implicated. Conclusion: Increased expression of Fascin1 and Pak1 enhances actin cytoskeleton remodeling in ABCs, promoting motility and antigen presentation. With these phenotypes, ABCs efficiently uptake and present antigens to T cells, and disperse easily within secondary lymphoid tissues.

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