2. Academic Validation
  3. Long-lived IgE plasma cells persist in secondary lymphoid tissues using a navitoclax-sensitive survival program

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

  • Immunity. 2025 Nov 11;58(11):2704-2716.e4. doi: 10.1016/j.immuni.2025.10.006.
Zhoujie Ding 1,  Mark R Dowling 2,  Adam K Wade-Vallance 3,  Alexandra R Dvorscek 1,  Catherine Pitt 1,  Jesse Mulder 1,  Kristy O'Donnell 1,  Craig McKenzie 1,  Alexandra Bosak Karaviotis 1,  Julia Scrofani 1,  Olaf Perdijk 1,  Danika L Hill 1,  Isaak Quast 1,  David M Tarlinton 1,  Christopher D C Allen 4,  Marcus J Robinson 5
Affiliations

Affiliations

  • 1 Department of Immunology, Monash University, Melbourne, VIC, Australia.
  • 2 Department of Clinical Haematology, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Parkville, VIC, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia; Cancer Immunology Division and Centre of Excellence for Cellular Immunotherapy, Peter MacCallum Cancer Centre, Melbourne, Australia.
  • 3 Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA, USA.
  • 4 Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA; Sandler Asthma Basic Research Center, University of California, San Francisco, San Francisco, CA, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA, USA.
  • 5 Department of Immunology, Monash University, Melbourne, VIC, Australia. Electronic address: [email protected].
PMID: 41192430 DOI: 10.1016/j.immuni.2025.10.006
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, BCLXL, and BCLW 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

ABT-263; BCL(XL); BCL2; IgE; MCL1; allergy; antibody-secreting cell; apoptosis; plasma cell; plasmablast.

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