Regulation of B cell fate by chronic activity of the IgE B cell receptor

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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.

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Zhiyong Yang

Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Marcus J Robinson

Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Xiangjun Chen

MOE Key Laboratory of Protein Sciences, Tsinghua University, Beijing, China

Competing interests
The authors declare that no competing interests exist.
Geoffrey Alexander Smith

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1638-4219
Jack Taunton

Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Wanli Liu

MOE Key Laboratory of Protein Sciences, Tsinghua University, Beijing, China

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0395-2800
Christopher DC Allen

Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States

For correspondence
Chris.Allen@ucsf.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1879-9047

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.

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.

Copyright

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.