Long-lived IgE plasma cells residing in the spleen contribute to the persistence of allergy 4302

Description IgE mediates allergic reactions due to its ability to bind to high affinity receptors on mast cells inducing degranulation upon crosslinking. IgE production is highly regulated and IgE plasma cells (PC) are rare. Most IgE PC are believed to be immature and short-lived. However, the sustained persistence of serum IgE in the absence of allergen exposure supports the existence of long-lived IgE PC (LLPC). Here we have characterized IgE PC in models of immunization and helminth infection using scRNAseq, spectral flow cytometry, and timestamping in a new Prdm1creERR26tdT mouse strain. We found that IgE PC are formed in an early wave after immunization or infection and unlike other PC, IgE PC undergo maturation into non-dividing MHCIIlow cells mainly in spleen and lymph nodes, and to much lower extent in the bone marrow. IgE PC are transcriptionally distinct from other PC: they display enhanced expression of translation, ER stress and glycosylation pathways. Nevertheless, as for other PC, maturation of IgE PC involves attenuation of those pathways and downregulation of the BCR. Mature IgE LLPC upregulate survival genes Tnfrsf17 (encoding BCMA), Tnfrsf13b (encoding TACI), Bcl2 and Mcl1, and express higher levels of Laptm5 and Atf5 than other PC. Phenotypically IgE LLPC can be identified as MHCIIlow/- CD93+. Our findings reveal that IgE PC mature and become LLPC residing mainly in the spleen. These findings offer new insights into the persistence of allergic responses. Funding Sources This work was supported by NIH grants R01AI151707 and R01AI153708 Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)