IgM and IgD B cell receptors differentially respond to endogenous antigens and control B cell fate
- University of California, San Francisco, United States
- UT Southwestern Medical Center, United States
- University at Buffalo, The State University of New York, United States
- International Center for Genetic Engineering and Biotechnology (ICGE), Cape Town, South Africa
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.
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Author details
Funding
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 A127648)
- Julie Zikherman
National Science Foundation (1650113)
- Mark Noviski
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of the University of California, San Francisco. The protocol was approved by the IACUC committee of the University of California, San Francisco (Protocol number: AN171020-01).
Copyright
© 2018, Noviski et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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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
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