Microbial symbionts regulate the primary Ig repertoire

The ability of immunoglobulin (Ig) to recognize pathogens is critical for optimal immune fitness. Early events that shape pre-immune Ig repertoires, expressed on IgM+ IgD+ B cells as B cell receptors (BCRs), are poorly defined. Here we studied germ-free mice and conventionalized littermates to explore the hypothesis that symbiotic microbes help shape the pre-immune Ig repertoire. Ig binding assays showed that exposure to conventional microbial symbionts enriched frequencies of anti-bacterial IgM+ IgD+ B cells in intestine and spleen. This enrichment affected follicular B cells, involving a diverse set of Ig variable region gene segments, and was T cell-independent. Functionally, enrichment of microbe reactivity primed basal levels of small intestinal T cell-independent symbiont-reactive IgA, and enhanced systemic IgG responses to bacterial immunization. These results demonstrate that microbial symbionts influence host immunity by enriching frequencies of anti-bacterial specificities within pre- immune B cell repertoires.