Long-lived IgE plasma cells persist in secondary lymphoid tissues using a navitoclax-sensitive survival program

Ding, Z; Dowling, MR; Wade-Vallance, AK; Dvorscek, AR; Pitt, C; Mulder, J; O&#39;Donnell, K; McKenzie, C; Karaviotis, AB; Scrofani, J; Perdijk, O; Hill, DL; Quast, I; Tarlinton, DM; Allen, CDC; Robinson, MJ

Author(s): Ding, Z; Dowling, MR; Wade-Vallance, AK; Dvorscek, AR; Pitt, C; Mulder, J; O'Donnell, K; McKenzie, C; Karaviotis, AB; Scrofani, J; Perdijk, O; Hill, DL; Quast, I; Tarlinton, DM; Allen, CDC; Robinson, MJ;
Details: Publication Year 2025-11-11,Volume 58,Issue #11,Page 2704-2716.e4
Journal Title: Immunity
Publication Type: Research article
Abstract: Long-term allergies can exhibit persistent concentrations of circulating immunoglobulin E (IgE). Here, we examined the lifespan of IgE antibody-secreting cells (ASCs) to determine whether the IgE that sustains allergies receives contributions from long-lived cells or relies more heavily on constant ASC production. In mouse aeroallergy, IgE ASCs localized to the lungs, mediastinal lymph nodes, spleen, and bone marrow (BM). IgE ASC production continued for months after allergen exposure ceased. We identified long-lived IgE ASCs residing predominantly outside the BM, with a half-life exceeding 49 days; in contrast, most IgE ASCs had a 3-day half-life. Long-lived IgE ASCs matured phenotypically, became quiescent, retained their surface B cell receptors, but showed low expression of the BM homing receptor CXCR4. They were hierarchically more reliant on the navitoclax-sensitive anti-apoptotic molecules BCL2, BCL(XL), and BCL(W) than MCL1. Thus, continual production of short-lived IgE ASCs and retention of long-lived IgE ASCs outside the BM together drive IgE persistence, perpetuating allergic disease.
Keywords: Animals; *Immunoglobulin E/immunology/metabolism; Mice; *Plasma Cells/immunology/drug effects; *Aniline Compounds/pharmacology; *Sulfonamides/pharmacology; *Hypersensitivity/immunology; Mice, Inbred C57BL; Receptors, CXCR4/metabolism; *Lymphoid Tissue/immunology; Proto-Oncogene Proteins c-bcl-2/metabolism; Cell Survival/immunology; Allergens/immunology; Abt-263; Bcl(xl); Bcl2; IgE; Mcl1; allergy; antibody-secreting cell; apoptosis; plasma cell; plasmablast
Department(s): Haematology; Laboratory Research
Publisher's Version: https://doi.org/10.1016/j.immuni.2025.10.006
Open Access at Publisher's Site: https://doi.org/10.1016/j.immuni.2025.10.006
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-12-04 05:58:01

Last Modified: 2025-12-04 05:59:00