Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 215, Issue 5, Pages 1397-1415Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20171761
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Funding
- National Institutes of Health [AI121394, AI1113217]
- Ruth L. Kirschstein National Research Service Award Institutional Research Training Grant [AI007306-31]
- National Council for Scientific and Technological Development (CNPq)/Science Without Borders Program, Brazil
- Burroughs Wellcome Fund
- Food Allergy Research & Education (FARE)
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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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