The constitutive presence of commensal bacteria contributes to the abundance of cecal IgG2b⁺ B cells and the supply of serum IgG2b reactive to commensal bacteria in adult mice

Abstract

Immunoglobulin (Ig) G isotypes in the sera of healthy mice and humans react to commensal bacteria. We previously reported that BALB/c mice with normal gut microbiota possessed abundant B cells that produced IgG2b reactive to commensal bacteria in cecal patches (CePs), indicating a potential source of a systemic pool of commensal bacteria-reactive IgG2b. Mice housed under germ-free conditions demonstrate the importance of the gut microbiota in driving cecal IgG2b responses. However, it is unclear whether the constitutive presence of the gut microbiota and specific bacterial taxa are important for IgG2b responses in adult mice. In this study, we showed that elimination of the gut microbiota by mixed antibiotic treatment in adult mice decreased the abundance of IgG2b⁺ B cells, follicular helper T (Tfh) cells in CePs, and the serum levels of commensal bacteria-reactive IgG2b. Reduced IgG2b responses have also been observed in mice with an altered gut microbiota following treatment with ampicillin or vancomycin. Changes in the diversity and composition of the cecal microbiota, particularly a decrease in Lachnospiraceae, Muribaculaceae, Ruminococcaceae, and Bacteroidaceae abundance at the family level, were observed in these mice. In addition, depletion of CD4⁺ T cells by the injection of neutralizing antibodies in adult mice reduced IgG2b responses. Our results suggest that specific gut bacteria susceptible to ampicillin and vancomycin play roles in providing an abundance of Tfh cells to help the generation of IgG2b⁺ B cells in CePs in adult mice, which may contribute to the supply of systemic commensal bacteria-reactive IgG2b.