1. Cell Biology
  2. Immunology and Inflammation
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Regulation of B cell fate by chronic activity of the IgE B cell receptor

  1. Zhiyong Yang
  2. Marcus J Robinson
  3. Xiangjun Chen
  4. Geoffrey Alexander Smith
  5. Jack Taunton
  6. Wanli Liu
  7. Christopher DC Allen  Is a corresponding author
  1. University of California, San Francisco, United States
  2. Tsinghua University, China
Research Article
  • Cited 40
  • Views 2,768
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Cite this article as: eLife 2016;5:e21238 doi: 10.7554/eLife.21238

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

  1. Zhiyong Yang

    Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. 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.
  3. Xiangjun Chen

    MOE Key Laboratory of Protein Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1638-4219
  5. 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.
  6. Wanli Liu

    MOE Key Laboratory of Protein Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0395-2800
  7. 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.
    ORCID icon "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.

Reviewing Editor

  1. Tomohiro Kurosaki, Osaka University, Japan

Publication history

  1. Received: September 4, 2016
  2. Accepted: December 8, 2016
  3. Accepted Manuscript published: December 9, 2016 (version 1)
  4. 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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