Long-lived antigen-induced IgM plasma cells demonstrate somatic mutations and contribute to long-term protection

Nat Commun. 2016 Jun 7;7:11826. doi: 10.1038/ncomms11826.

Abstract

Long-lived plasma cells are critical to humoral immunity as a lifelong source of protective antibodies. Antigen-activated B cells-with T-cell help-undergo affinity maturation within germinal centres and persist as long-lived IgG plasma cells in the bone marrow. Here we show that antigen-specific, induced IgM plasma cells also persist for a lifetime. Unlike long-lived IgG plasma cells, which develop in germinal centres and then home to the bone marrow, IgM plasma cells are primarily retained within the spleen and can develop even in the absence of germinal centres. Interestingly, their expressed IgV loci exhibit somatic mutations introduced by the activation-induced cytidine deaminase (AID). However, these IgM plasma cells are probably not antigen-selected, as replacement mutations are spread through the variable segment and not enriched within the CDRs. Finally, antibodies from long-lived IgM plasma cells provide protective host immunity against a lethal virus challenge.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer
  • Amino Acid Motifs
  • Animals
  • Antigens / immunology*
  • Complementarity Determining Regions / genetics
  • Cytidine Deaminase / chemistry
  • Cytidine Deaminase / genetics
  • Germinal Center / cytology
  • Immunity*
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin M / immunology*
  • Mice, Inbred C57BL
  • Mutation / genetics*
  • Neutralization Tests
  • Orthomyxoviridae / immunology
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / virology
  • Plasma Cells / immunology*
  • Somatic Hypermutation, Immunoglobulin / genetics
  • Spleen / cytology

Substances

  • Antigens
  • Complementarity Determining Regions
  • Immunoglobulin Heavy Chains
  • Immunoglobulin M
  • Cytidine Deaminase