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

SUMMARY IgE plasma cells (PC) producing high affinity antibodies are critical players in allergic diseases. Allergies may persist or resolve over time, but the factors involved in their evolution are not well known. Sustained production of IgE antibodies, even in the absence of allergen exposure in persistent allergy, suggests the existence of long-lived IgE PC. However, the ability of IgE PC to undergo terminal differentiation and become long-lived has been questioned. Here we demonstrate that IgE PC undergo swift maturation into non-dividing MHCII low CD93 + CD98 high PC in immunized mice. Mature IgE PC have a distinct transcriptional profile for adaptation to high protein synthesis, glycosylation, and survival. Using PC timestamping, long-lived IgE PC could be found several months after immunization in mice. Remarkably, the spleen rather than the bone marrow, was a main tissue of residence of mature long-lived IgE PC. Our findings provide key insights to understand IgE production in persistent allergy. Highlights IgE PC form in a narrow window after immunization and undergo swift maturation. Timestamping reveals the existence of CD93 + CD98 high MHCII low long-lived IgE PC. The spleen and lymph nodes are the main tissues of mature IgE PC residence. IgE PC use distinct adaptations to high antibody secretion and survival.