A mechanism for the elimination of IgE plasma cells

Abstract

The proper regulation of IgE production safeguards against allergic disease, yet the mechanisms that restrict IgE plasma cell (PC) longevity are unclear. Here, we demonstrated that high surface B cell receptor (BCR) expression on IgE PCs corresponded with the phosphorylation of BCR signalosome proteins following cognate antigen exposure. Within hours of BCR stimulation in cell culture, IgE PCs lost surface CD138 expression and underwent cell death. This depletion of IgE PCs correlated with the affinity, avidity, amount, and duration of antigen exposure and required Syk, BLNK, and PLCγ2. In mice with a PC-specific impairment of BCR signaling, the abundance of IgE PCs was selectively increased. Conversely, after IgE BCR ligation with a monoclonal antibody, IgE PCs were depleted in vitro and in vivo. These findings establish that IgE PC longevity is constrained by BCR stimulation, which may contribute to the mechanisms of allergen tolerance and immunotherapy as well as anti-IgE monoclonal antibody treatments.