Single-cell mapping of human plasma cell fate reveals a commitment checkpoint and Cav-1β expression associated with mTORC1 machinery
Abstract
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.
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BibTeX
@article{caron2026singlecell,
title = {{Single-cell mapping of human plasma cell fate reveals a commitment checkpoint and Cav-1β expression associated with mTORC1 machinery}},
author = {Gersende Caron and Fabienne Desmots and Mélanie Chabaud and Maud Lemarié and Vincent Olivier and Fabrice Chatonnet and Céline Nonn and Cassandra Jadeau and Simon Léonard and Céline Monvoisin and Kathleen Santamaria and Cédric M. Blouin and Noudjoud Attaf and Tarek Gharsalli and Pierre Milpied and Christophe Lamaze and Céline Pangault and Marion Haas and Thierry Fest},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117865},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03248-7},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Single-cell mapping of human plasma cell fate reveals a commitment checkpoint and Cav-1β expression associated with mTORC1 machinery
AU - Gersende Caron
AU - Fabienne Desmots
AU - Mélanie Chabaud
AU - Maud Lemarié
AU - Vincent Olivier
AU - Fabrice Chatonnet
AU - Céline Nonn
AU - Cassandra Jadeau
AU - Simon Léonard
AU - Céline Monvoisin
AU - Kathleen Santamaria
AU - Cédric M. Blouin
AU - Noudjoud Attaf
AU - Tarek Gharsalli
AU - Pierre Milpied
AU - Christophe Lamaze
AU - Céline Pangault
AU - Marion Haas
AU - Thierry Fest
PY - 2026
DA - 2026/10/13
JO - iScience
DO - 10.1016/j.isci.2026.117865
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03248-7
AB - 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.
SN - 2589-0042
ER -