Title: Neonatal Exposure to Commensal-Bacteria-Derived Antigens Directs Polysaccharide-Specific B-1 B Cell Repertoire Development
Author: J. Stewart New, Brian L.P. Dizon, Christopher F. Fucile, Alexander F. Rosenberg, John F. Kearney, R. Glenn King
Abstract: B-1 B cells derive from a developmental program distinct from that of conventionalB cells, through B cell receptor (BCR)-dependent positive selection of fetally derivedprecursors. Here, we used direct labeling of B cells reactive with the N-acetyl-D-glucosamine(GlcNAc)-containing Lancefield group A carbohydrate of Streptococcus pyogenes to study the effects of bacterial antigens on the emergent B-1 B cell clonal repertoire.The number, phenotype, and BCR clonotypes of GlcNAc-reactive B-1 B cells were modulatedby neonatal exposure to heat-killed S. pyogenes bacteria. GlcNAc-reactive B-1 clonotypes and serum antibodies were reduced in germ-freemice compared with conventionally raised mice. Colonization of germ-free mice witha conventional microbiota promoted GlcNAc-reactive B-1 B cell development and concomitantlyelicited clonally related IgA+ plasma cells in the small intestine. Thus, exposure to microbial antigens in earlylife determines the clonality of the mature B-1 B cell repertoire and ensuing antibodyresponses, with implications for vaccination approaches and schedules.