BALB/c and C57BL/6 Mice Differ in Polyreactive IgA Abundance, which Impacts the Generation of Antigen-Specific IgA and Microbiota Diversity

Immunity. 2015 Sep 15;43(3):527-40. doi: 10.1016/j.immuni.2015.08.011. Epub 2015 Sep 8.

Abstract

The interrelationship between IgAs and microbiota diversity is still unclear. Here we show that BALB/c mice had higher abundance and diversity of IgAs than C57BL/6 mice and that this correlated with increased microbiota diversity. We show that polyreactive IgAs mediated the entrance of non-invasive bacteria to Peyer's patches, independently of CX3CR1(+) phagocytes. This allowed the induction of bacteria-specific IgA and the establishment of a positive feedback loop of IgA production. Cohousing of mice or fecal transplantation had little or no influence on IgA production and had only partial impact on microbiota composition. Germ-free BALB/c, but not C57BL/6, mice already had polyreactive IgAs that influenced microbiota diversity and selection after colonization. Together, these data suggest that genetic predisposition to produce polyreactive IgAs has a strong impact on the generation of antigen-specific IgAs and the selection and maintenance of microbiota diversity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology*
  • Bacteria / classification
  • Bacteria / genetics
  • Bacteria / immunology
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • Feces / microbiology
  • Flow Cytometry
  • Genetic Variation / immunology*
  • Host-Pathogen Interactions / immunology
  • Immunization
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology*
  • Immunoglobulin A / metabolism
  • Metagenomics / methods
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Microbiota / genetics
  • Microbiota / immunology*
  • Peyer's Patches / immunology
  • Peyer's Patches / metabolism
  • Peyer's Patches / microbiology
  • Phylogeny
  • RNA, Ribosomal, 16S / genetics
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / immunology
  • Salmonella typhimurium / physiology
  • Species Specificity

Substances

  • Antigens, Bacterial
  • DNA, Bacterial
  • Immunoglobulin A
  • RNA, Ribosomal, 16S