Age, microbiota, and T cells shape diverse individual IgA repertoires in the intestine

J Exp Med. 2012 Feb 13;209(2):365-77. doi: 10.1084/jem.20111980. Epub 2012 Jan 16.


Intestinal immunoglobulin A (IgA) ensures host defense and symbiosis with our commensal microbiota. Yet previous studies hint at a surprisingly low diversity of intestinal IgA, and it is unknown to what extent the diverse Ig arsenal generated by somatic recombination and diversification is actually used. In this study, we analyze more than one million mouse IgA sequences to describe the shaping of the intestinal IgA repertoire, its determinants, and stability over time. We show that expanded and infrequent clones combine to form highly diverse polyclonal IgA repertoires with very little overlap between individual mice. Selective homing allows expanded clones to evenly seed the small but not large intestine. Repertoire diversity increases during aging in a dual process. On the one hand, microbiota-, T cell-, and transcription factor RORγt-dependent but Peyer's patch-independent somatic mutations drive the diversification of expanded clones, and on the other hand, new clones are introduced into the repertoire of aged mice. An individual's IgA repertoire is stable and recalled after plasma cell depletion, which is indicative of functional memory. These data provide a conceptual framework to understand the dynamic changes in the IgA repertoires to match environmental and intrinsic stimuli.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology*
  • Analysis of Variance
  • Animals
  • Base Sequence
  • Cluster Analysis
  • Complementarity Determining Regions / genetics
  • DNA Primers / genetics
  • Enzyme-Linked Immunospot Assay
  • Flow Cytometry
  • Genetic Variation / immunology*
  • Immunoglobulin A / genetics*
  • Immunoglobulin A / immunology
  • Intestine, Small / immunology*
  • Intestine, Small / microbiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Phylogeny
  • Receptors, CCR / genetics
  • Receptors, CCR / metabolism
  • Sequence Analysis, DNA
  • Somatic Hypermutation, Immunoglobulin / genetics*
  • T-Lymphocytes / immunology*


  • CC chemokine receptor 9
  • Complementarity Determining Regions
  • DNA Primers
  • Immunoglobulin A
  • Receptors, CCR