Single-cell mapping of human plasma cell fate reveals a commitment checkpoint and Cav-1β expression associated with...

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.