Lambda light chain revision in the human intestinal IgA response

J Immunol. 2008 Jul 15;181(2):1264-71. doi: 10.4049/jimmunol.181.2.1264.

Abstract

Revision of Ab L chains by secondary rearrangement in mature B cells has the potential to change the specific target of the immune response. In this study, we show for the first time that L chain revision is normal and widespread in the largest Ab producing population in man: intestinal IgA plasma cells (PC). Biases in the productive and non-productive repertoire of lambda L chains, identification of the circular products of rearrangement that have the characteristic biases of revision, and identification of RAG genes and protein all reflect revision during normal intestinal IgA PC development. We saw no evidence of IgH revision, probably due to inappropriately orientated recombination signal sequences, and little evidence of kappa-chain revision, probably due to locus inactivation by the kappa-deleting element. We propose that the lambda L chain locus is available and a principal modifier and diversifier of Ab specificity in intestinal IgA PCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Diversity
  • Antibody Specificity
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism*
  • Gene Rearrangement, B-Lymphocyte, Light Chain*
  • Genes, Immunoglobulin
  • Humans
  • Immunoglobulin A / genetics*
  • Immunoglobulin A / immunology
  • Immunoglobulin kappa-Chains / genetics
  • Immunoglobulin kappa-Chains / immunology
  • Immunoglobulin lambda-Chains / genetics*
  • Immunoglobulin lambda-Chains / immunology
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Nuclear Proteins / immunology
  • Nuclear Proteins / metabolism*
  • Plasma Cells / immunology*
  • Plasma Cells / metabolism
  • Somatic Hypermutation, Immunoglobulin

Substances

  • DNA-Binding Proteins
  • Immunoglobulin A
  • Immunoglobulin kappa-Chains
  • Immunoglobulin lambda-Chains
  • Nuclear Proteins
  • RAG2 protein, human