Self-Restrained B Cells Arise following Membrane IgE Expression

Among immunoglobulins (Igs), IgE can powerfully contribute to antimicrobial immunity and severe allergy despite its low abundance. IgE protein and gene structure resemble other Ig classes, making it unclear what constrains its production to thousand-fold lower levels. Whether class-switched B cell receptors (BCRs) differentially control B cell fate is debated, and study of the membrane (m)IgE class is hampered by its elusive in vivo expression. Here, we demonstrate a self-controlled mIgE+ B cell stage. Primary or transfected mIgE+ cells relocate the BCRs into spontaneously internalized lipid rafts, lose mobility to chemokines, and change morphology. We suggest that combined proapoptotic mechanisms possibly involving Hax1 prevent mIgE+ memory lymphocyte accumulation. By uncoupling in vivo IgE switching from cytokine and antigen stimuli, we show that these features are independent from B cell stimulation and instead result from mIgE expression per se. Consequently, few cells survive IgE class switching, which might ensure minimal long-term IgE memory upon differentiation into plasma cells. [Display omitted] •Membrane IgE appears transiently and is then internalized•The IgE B cell receptor (BCR) spontaneously co-localizes with lipid rafts•IgE BCR expression restrains mobility responses to chemokines•mIgE promotes apoptosis of IgE+ cells, severely impacting their fate IgE responses may convey severe allergy and thus need tight control. Laffleur et al. demonstrate a self-restrained B cell stage where membrane IgE expression impacts the phenotype, shape, and mobility of B lymphocytes, promotes apoptosis, and severely shortens IgE+ B cell fate.