A distinct TCR+CD19+ population in the peritoneal cavity: B1a cells as precursors of extrathymic T cells

Abstract

The precise ontogeny of extrathymic T cells remains elusive, and the potential contribution of self-renewing B1 cells to T cell generation has not been defined. Here, we identify a distinct population of TCR+CD19+ double-positive (DP) cells in the peritoneal cavity that serves as a developmental intermediate between B1a cells and extrathymic T cells. These DP cells originated from CD19+ B lineage cells and were highly enriched within the CD5+CD43+ B1a subset. Phenotypic and t-SNE analyses revealed ordered transitional states characterized by progressive acquisition of T lineage features. In vivo adoptive transfer and in vitro co-culture assays demonstrated that B1a cells generated functional extrathymic T cells, a process promoted by Notch signaling and IL-2 family cytokines. During this process, B1a-derived cells underwent transient Rag reactivation and TCR rearrangement and acquired canonical effector functions, including cytokine production and cytotoxicity. These findings uncover B1a lineage plasticity and define an unrecognized pathway of extrathymic T lymphopoiesis.