B cells shape naive CD8+ T cell programming.

The presence of B cells is essential for the formation of CD8+ T cell memory after infection and vaccination. In this study, we investigated whether B cells influence the programming of naive CD8+ T cells prior to their involvement in an immune response. RNA sequencing indicated that B cells are necessary for sustaining the FOXO1-controlled transcriptional program, which is critical for homeostasis of these T cells. Without an appropriate B cell repertoire, mouse naive CD8+ T cells exhibit a terminal, effector-skewed phenotype, which significantly impacts their response to vaccination. A similar effector-skewed phenotype with reduced FOXO1 expression was observed in naive CD8+ T cells from human patients undergoing B cell-depleting therapies. Furthermore, we show that patients without B cells have a defect in generating long-lived CD8+ T cell memory following COVID vaccination. In summary, we demonstrate that B cells promote the quiescence of naive CD8+ T cells, poising them to become memory cells upon vaccination.