Long-lived IgE plasma cells that reside in the spleen contribute to the persistence of the IgE response.

Expression of the IgE BCR is associated with increased B cell apoptosis, yet in persistent allergy, sustained production of IgE antibodies in the absence of allergen exposure suggests the existence of long-lived IgE plasma cells (PCs). Here we studied the development and localization of IgE PCs in mouse models of allergy. After immunization, IgE PCs underwent maturation in spleen and lymph nodes, acquiring a stable MHCIIloCD93+CD98hiBCRlo phenotype. Mature IgE PCs had a distinct transcriptional profile adapted to high protein synthesis, glycosylation, and survival and resisted BCR-crosslinking-induced apoptosis. Immunization induced a burst of short-lived IgE PC formation, followed by a reduced differentiation rate over time, compared with IgG1 PCs. Timestamping of PCs revealed long-lived IgE PCs that localize to the spleen, in addition to the bone marrow (BM). Thus, immune challenge can generate both short-lived and long-lived IgE PCs, with long-lived IgE PCs in spleen and BM contributing to allergy persistence.