Regulation of B cell fate by chronic activity of the IgE B cell receptor
Zhiyong Yang,
Marcus J Robinson,
Xiangjun Chen,
Geoffrey A Smith,
Jack Taunton,
Wanli Liu,
Christopher D C Allen
Affiliations
Zhiyong Yang
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
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
Xiangjun Chen
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
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
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
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.
