Single-cell mapping of human plasma cell fate reveals a commitment checkpoint and Cav-1β expression associated with mTORC1 machinery
Human B cell differentiation into antibody-secreting plasma cells (PCs) requires coordinated transcriptional and organelle remodeling. Using single-cell transcriptomics in an in vitro human B cell differentiation system, we identified a Day-8 commitment checkpoint separating PC, memory B cell, and germinal center-like trajectories and defined an XBP1-associated transcriptional program linked to organelle remodeling. Within this program, CAV1 was induced during PC commitment and encoded a non-caveolar Cav-1β isoform expressed in plasmablasts and PCs. Proteomic analyses showed that Cav-1β associates with endoplasmic reticulum, secretory, and nutrient-sensing proteins, including components of the V-ATPase-RAGulator-RAG complex. CAV1 silencing had modest effects on PC differentiation but did not alter acute mTORC1 activation or antibody secretion. These findings place Cav-1β within the membrane and organelle remodeling program of human PCs and highlight how intracellular architecture may be coupled to metabolic and secretory adaptation during plasma cell differentiation.
Authors
- Tarek Gharsalli (ORCID: https://orcid.org/0000-0002-4038-8447)
- Céline Monvoisin (ORCID: https://orcid.org/0000-0003-1511-7888)
- Céline Pangault (ORCID: https://orcid.org/0000-0003-3978-2209)
- Maud Lemarié
- Kathleen Santamaria (ORCID: https://orcid.org/0000-0001-7301-0136)
- Céline Nonn
- Thierry Fest (ORCID: https://orcid.org/0000-0002-6437-4189)
- Fabrice Chatonnet (ORCID: https://orcid.org/0000-0003-3639-6775)
- Simon Léonard (ORCID: https://orcid.org/0000-0002-6437-5800)
- Mélanie Chabaud (ORCID: https://orcid.org/0000-0003-3167-7076)
- Cassandra Jadeau (ORCID: https://orcid.org/0009-0004-2016-7278)
- Vincent Olivier
- Noudjoud Attaf
- Marion Haas
- Fabienne Desmots
- Gersende Caron
- Pierre Milpied
- Christophe Lamaze
- Cédric M. Blouin
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Aix-Marseille Université (FR)
- Université Paris Sciences et Lettres (FR)
- Établissement Français du Sang (FR)
- Centre d’Immunologie de Marseille-Luminy (FR)
- Centre Hospitalier Universitaire de Rennes (FR)
- Chimie et Biologie de la Cellule (FR)
- Institut Curie (FR)
Publication Details
- Journal
- iScience
- Published
- 2026-10-13
- DOI
- https://doi.org/10.1016/j.isci.2026.117865
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Agence Nationale de la Recherche
- Fondation Bettencourt Schueller