Regulation of B cell fate by chronic activity of the IgE B cell receptor
Abstract
IgE can trigger potent allergic responses, yet the mechanisms regulating IgE production are poorly understood. Here we reveal that IgE+ B cells are constrained by chronic activity of the IgE B cell receptor (BCR). In the absence of cognate antigen, the IgE BCR promoted terminal differentiation of B cells into plasma cells (PCs) under cell culture conditions mimicking T cell help. This antigen-independent PC differentiation involved multiple IgE domains and Syk, CD19, BLNK, Btk, and IRF4. Disruption of BCR signaling in mice led to consistently exaggerated IgE+ germinal center (GC) B cell but variably increased PC responses. We were unable to confirm reports that the IgE BCR directly promoted intrinsic apoptosis. Instead, IgE+ GC B cells exhibited poor antigen presentation and prolonged cell cycles, suggesting reduced competition for T cell help. We propose that chronic BCR activity and access to T cell help play critical roles in regulating IgE responses.
Article and author information
Author details
Funding
Sandler Asthma Basic Research Center
- Zhiyong Yang
- Marcus J Robinson
- Christopher DC Allen
Weston Havens Foundation
- Christopher DC Allen
National Institute of Allergy and Infectious Diseases (F30AI120517)
- Geoffrey Alexander Smith
Pew Charitable Trusts
- Christopher DC Allen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Tomohiro Kurosaki, Osaka University, Japan
Ethics
Animal experimentation: The care, maintenance, and experimental manipulation of mice followed guidelines established by the by the Institutional Animal Care and Use Committee of the University of California, San Francisco under approved protocols AN089524 and AN111286.
Version history
- Received: September 4, 2016
- Accepted: December 8, 2016
- Accepted Manuscript published: December 9, 2016 (version 1)
- Version of Record published: January 3, 2017 (version 2)
Copyright
© 2016, Yang 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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