IgM and igD b cell receptors differentially respond to endogenous antigens and control B cell fate

Mark Noviski, James L. Mueller, Anne Satterthwaite, Lee Ann Garrett-Sinha, Frank Brombacher, Julie Zikherman

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Naive B cells co-express two BCR isotypes, IgM and IgD, with identical antigen-binding domains but distinct constant regions. IgM but not IgD is downregulated on autoreactive B cells. Because these isotypes are presumed to be redundant, it is unknown how this could impose tolerance. We introduced the Nur77-eGFP reporter of BCR signaling into mice that express each BCR isotype alone. Despite signaling strongly in vitro, IgD is less sensitive than IgM to endogenous antigen in vivo and developmental fate decisions are skewed accordingly. IgD-only Lyn/ B cells cannot generate autoantibodies and short-lived plasma cells (SLPCs) in vivo, a fate thought to be driven by intense BCR signaling induced by endogenous antigens. Similarly, IgD-only B cells generate normal germinal center, but impaired IgG1+ SLPC responses to T-dependent immunization. We propose a role for IgD in maintaining the quiescence of autoreactive B cells and restricting their differentiation into autoantibody secreting cells.

Original languageEnglish (US)
Article numbere35074
JournaleLife
Volume7
DOIs
StatePublished - Mar 9 2018

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Noviski, M., Mueller, J. L., Satterthwaite, A., Garrett-Sinha, L. A., Brombacher, F., & Zikherman, J. (2018). IgM and igD b cell receptors differentially respond to endogenous antigens and control B cell fate. eLife, 7, [e35074]. https://doi.org/10.7554/eLife.35074