Naive B Cells with High-Avidity Germline-Encoded Antigen Receptors Produce Persistent IgM+ and Transient IgG+ Memory B Cells

Immunity. 2018 Jun 19;48(6):1135-1143.e4. doi: 10.1016/j.immuni.2018.04.019. Epub 2018 Jun 5.

Abstract

Although immune memory often lasts for life, this is not the case for certain vaccines in some individuals. We sought a mechanism for this phenomenon by studying B cell responses to phycoerythrin (PE). PE immunization of mouse strains with Ighb immunoglobulin (Ig) variable heavy chain (VH) genes elicited affinity-matured switched Ig memory B cells that declined with time, while the comparable population from an Igha strain was numerically stable. Ighb strains had larger numbers of PE-specific naive B cells and generated smaller germinal center responses and larger numbers of IgM memory cells than the Igha strain. The properties of PE-specific B cells in Ighb mice correlated with usage of a single VH that afforded high-affinity PE binding in its germline form. These results suggest that some individuals may be genetically predisposed to generate non-canonical memory B cell responses to certain antigens because of avid antigen binding via germline-encoded VH elements.

Keywords: V(H); memory B cell; naive B cell; repertoire.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Genes, Immunoglobulin
  • Immunoglobulin G / genetics
  • Immunoglobulin G / immunology*
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin M / genetics
  • Immunoglobulin M / immunology*
  • Immunoglobulin Variable Region / genetics
  • Immunologic Memory / genetics*
  • Immunologic Memory / immunology*
  • Mice
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / immunology*

Substances

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