A mechanism for the elimination of IgE plasma cells

Abstract

The proper regulation of IgE production safeguards against allergic disease, highlighting the importance of mechanisms that restrict IgE plasma cell (PC) survival. IgE PCs have unusually high surface B cell receptor (BCR) expression, yet the functional consequences of ligating this receptor are unknown. Here, we found that BCR ligation induced BCR signaling in IgE PCs followed by their elimination. In cell culture, exposure of IgE PCs to cognate antigen or anti-BCR antibodies induced apoptosis. IgE PC depletion correlated with the affinity, avidity, amount, and duration of antigen exposure and required the BCR signalosome components Syk, BLNK, and PLCγ2. In mice with a PC-specific impairment of BCR signaling, the abundance of IgE PCs was selectively increased. Conversely, BCR ligation by injection of cognate antigen or anti-IgE depleted IgE PCs. These findings establish a mechanism for the elimination of IgE PCs through BCR ligation. This has important implications for allergen tolerance and immunotherapy as well as anti-IgE monoclonal antibody treatments.This research was supported by the National Institute of Allergy and Infections Diseases of the National Institutes of Health under Award Number R01AI130470; the Program for Breakthrough Biomedical Research, which is partially funded by the Sandler Foundation; the Sandler Asthma Basic Research Center; and the Cardiovascular Research Institute at the University of California, San Francisco. C.D.C.A. was a Pew Scholar in the Biomedical Sciences, supported by The Pew Charitable Trusts. A.K.W-V was supported by a Doctoral Foreign Study Award from the Canadian Institute of Health Research, funding reference number DFD-170769. D.M.T. and M.J.R. were funded by National Health and Medical Research Council (NHMRC) Australia by an Investigator Award (APP1175411) and Ideas Grant (APP1185294), respectively. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.