B cells shape naïve CD8 T cell programming

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Abstract

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 naïve 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 their homeostasis. Without an appropriate B cell repertoire, mouse naïve 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 naïve 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 naïve CD8 T cells, poising them to become memory cells upon vaccination.

Authors

Cameron Manes, Miguel Guerrero Moreno, Jennifer Cimons, Marc A. D'Antonio, Tonya M. Brunetti, Michael G. Harbell, Sean Selva, Christopher Mizenko, Tyler L. Borko, Erika L. Lasda, Jay R. Hesselberth, Elena W.Y. Hsieh, Michael R. Verneris, Amanda L. Piquet, Laurent Gapin, Ross M. Kedl, Jared Klarquist