title: 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.
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.|Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, United States.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.|Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, United States.
authors.forename: Marcus J
authors.identifier: 0000-0001-5677-3078
authors.initials: MJ
authors.lastname: Robinson
authors.affiliation: 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.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States.
authors.forename: Geoffrey A
authors.identifier: 0000-0002-1638-4219
authors.initials: GA
authors.lastname: Smith
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States.
authors.forename: Jack
authors.initials: J
authors.lastname: Taunton
authors.affiliation: 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.
authors.forename: Wanli
authors.identifier: 0000-0003-0395-2800
authors.initials: W
authors.lastname: Liu
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States.|Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, United States.|Department of Anatomy, University of California, San Francisco, San Francisco, United States.
authors.forename: Christopher D C
authors.identifier: 0000-0002-1879-9047
authors.initials: CD
authors.lastname: Allen
mesh_terms: D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D007073:Immunoglobulin E / Q000378:metabolism*; D008213:Lymphocyte Activation; D008810:Mice, Inbred C57BL; D017455:Receptors, IgE / Q000378:metabolism*
chemical_list: D017455:Receptors, IgE; D007073:Immunoglobulin E
keywords: B cell receptor; T cell help; antigen presentation; cell biology; germinal center; immunology; mouse; plasma cell; signaling