Mucosal tissue cues shape B cell memory through the IgA BCR
B cells generate plasma cells (PCs) and memory B cells (MBCs) to combat recurrent pathogens. B cell receptor (BCR) affinity dictates fate decisions in response to model antigens, but the factors regulating B cell fate during infection remain unknown. Here, we used respiratory and gastrointestinal infection models to study B cell selection across barrier tissues in mice. Memory selection was governed by tissue-specific cues: Selection in the lung was skewed toward MBCs, whereas the gut favored PC entry, even in response to the same pathogen. Divergence was linked to differential BCR isotype usage across barrier tissues rather than differential affinity maturation. In the gut, the commensal-induced TGF-β-rich milieu promoted class-switching to IgA, which skewed selection toward PCs, a process that was counteracted by the IgA cytosolic tail domain. Thus, mucosal B cell selection integrates tissue-specific cues by relying on BCR isotype usage, with implications for nasal and oral vaccine development.
Authors
- Claude Grégoire (ORCID: https://orcid.org/0000-0003-3302-5274)
- Mauro Gaya (ORCID: https://orcid.org/0000-0002-7535-8678)
- Ana Zarubica (ORCID: https://orcid.org/0000-0001-5488-4137)
- Michel Cogné (ORCID: https://orcid.org/0000-0002-8519-4427)
- Michelle A. Linterman (ORCID: https://orcid.org/0000-0001-6047-1996)
- Emma Slack (ORCID: https://orcid.org/0000-0002-2473-1145)
- Apurwa Trivedi (ORCID: https://orcid.org/0000-0002-9923-7440)
- María Pía Holgado
- Myriam Moussa
- Samuel Origlio
- Lucas Bertoia
- Frédéric FIORE (ORCID: https://orcid.org/0000-0001-7955-6594)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Babraham Institute (GB)
- Inserm (FR)
- Malaghan Institute of Medical Research (NZ)
- Aix-Marseille Université (FR)
- Université Rennes 2 (FR)
- ETH Zurich (CH)
- University of Oxford (GB)
- Institute for Biomedical Engineering (CH)
- Centre d’Immunologie de Marseille-Luminy (FR)
- Institute of Molecular and Clinical Ophthalmology Basel (CH)
- Université de Rennes (FR)
Publication Details
- Journal
- Science Immunology
- Published
- 2026-07-17
- DOI
- https://doi.org/10.1126/sciimmunol.adv1149
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Centre d'immunologie de Marseille-Luminy
- Miyuki Giken
- Conseil National de la Recherche Scientifique
- Association Neurofibromatoses et Recklinghause
- Egerton University
- European Research Council