Microbial symbionts regulate the primary Ig repertoire

Y Chen, N Chaudhary, N Yang, A Granato… - Journal of Experimental …, 2018 - rupress.org
Y Chen, N Chaudhary, N Yang, A Granato, JA Turner, SL Howard, C Devereaux, T Zuo…
Journal of Experimental Medicine, 2018rupress.org
The ability of immunoglobulin (Ig) to recognize pathogens is critical for optimal immune
fitness. Early events that shape preimmune 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 preimmune Ig repertoire. Ig-binding assays showed that exposure to conventional
microbial symbionts enriched frequencies of antibacterial IgM+ IgD+ B cells in intestine and …
The ability of immunoglobulin (Ig) to recognize pathogens is critical for optimal immune fitness. Early events that shape preimmune 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 preimmune Ig repertoire. Ig-binding assays showed that exposure to conventional microbial symbionts enriched frequencies of antibacterial 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 antibacterial specificities within preimmune B cell repertoires and that this may have consequences for mucosal and systemic immunity.
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