Microbial symbionts regulate the primary Ig repertoire

J Exp Med. 2018 May 7;215(5):1397-1415. doi: 10.1084/jem.20171761. Epub 2018 Mar 27.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • Bacteria / metabolism*
  • Clone Cells
  • Germ-Free Life
  • Immunity, Mucosal
  • Immunoglobulin Heavy Chains / metabolism
  • Immunoglobulin Variable Region / metabolism
  • Immunoglobulins / metabolism*
  • Intestine, Small / microbiology
  • Mice, Inbred C57BL
  • Receptors, Antigen, B-Cell / metabolism
  • Spleen / cytology
  • Symbiosis*
  • T-Lymphocytes / cytology

Substances

  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Immunoglobulins
  • Receptors, Antigen, B-Cell

Associated data

  • GENBANK/MG675261
  • GENBANK/MG675436