Format

Send to

Choose Destination
Elife. 2016 Dec 9;5. pii: e21238. doi: 10.7554/eLife.21238.

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

Author information

1
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.
2
Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, United States.
3
MOE Key Laboratory of Protein Sciences, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Life Sciences, Institute for Immunology, Tsinghua University, Beijing, China.
4
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States.
5
Department of Anatomy, University of California, San Francisco, San Francisco, United States.

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.

KEYWORDS:

B cell receptor; T cell help; antigen presentation; cell biology; germinal center; immunology; mouse; plasma cell; signaling

PMID:
27935477
PMCID:
PMC5207771
DOI:
10.7554/eLife.21238
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center