Immunity
Volume 53, Issue 1, 14 July 2020, Pages 172-186.e6
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Article
Neonatal Exposure to Commensal-Bacteria-Derived Antigens Directs Polysaccharide-Specific B-1 B Cell Repertoire Development

https://doi.org/10.1016/j.immuni.2020.06.006Get rights and content
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Highlights

  • GAC-reactive B cells exhibit the phenotype and localization patterns of B-1 B cells

  • Neonatal S. pyogenes immunization expands minor IGHV7-3 GAC-reactive BCR clonotypes

  • Establishment of IGHV6-3 GAC-reactive B cell clonal dominance is microbiota dependent

  • Microbiota-dependent expansion of GAC-reactive B cells seeds the SI LP with ASCs

Summary

B-1 B cells derive from a developmental program distinct from that of conventional B cells, through B cell receptor (BCR)-dependent positive selection of fetally derived precursors. 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 modulated by neonatal exposure to heat-killed S. pyogenes bacteria. GlcNAc-reactive B-1 clonotypes and serum antibodies were reduced in germ-free mice compared with conventionally raised mice. Colonization of germ-free mice with a conventional microbiota promoted GlcNAc-reactive B-1 B cell development and concomitantly elicited clonally related IgA+ plasma cells in the small intestine. Thus, exposure to microbial antigens in early life determines the clonality of the mature B-1 B cell repertoire and ensuing antibody responses, with implications for vaccination approaches and schedules.

Keywords

natural antibodies
B-1 B cells
neonatal immunity
Streptococcus pyogenes
N-acetyl-D-glucosamine
microbiota
B cell repertoire
innate-like B cells
Lancefield group A carbohydrate

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