B cells shape naive CD8 T cell programming and fate decisions

Abstract

Abstract Renewed interest in the relationship between B cells and CD8 T cells has revealed direct interactions between these cells, despite long-prevailing views that they function independently from one another. In fact, an IL-21-producing “helper” CD8 T cell subset has been described; yet, whether B cells have the reciprocal capacity to support CD8 T cells is less well-studied. Here, we find B cells influence the phenotype of naive, effector, and memory CD8 T cells. In MD4 mice, which have a fixed BCR repertoire, naive CD8 T cells exhibit an activated/effector phenotype, including relatively high pAkt, p70-s6K, and 4e-bp1, and low Foxo1 and Eomes. Primary CD8 T cell responses to subunit vaccination in MD4 or B cell-deficient mice are numerically reduced and effector-skewed. Importantly, the magnitude and function of memory CD8 T cells 3 months after vaccination are impaired in MD4 mice, leading to increased susceptibility to bacterial challenge. Adoptive transfer of CD8 T cells from WT into MD4 mice results in a similar effector-skewing upon vaccination, demonstrating that these phenotypic changes result from T cell-extrinsic factors. Furthermore, CAR T cell-mediated B cell depletion in 6-week-old WT mice also recapitulated the reductions in primary CD8 T cell numbers and their effector-skewing after vaccination. In agreement with prior literature, peak T cell responses after Listeria m. infection are of equivalent magnitude in WT and B cell-deficient mice, yet here we also observe reductions in their CD127+ memory phenotype. Together, these data indicate that B cells perform an important, broad role in the establishment of the naive CD8 T cell pool and subsequent regulation of CD8 T cell programming following subunit vaccination or infection.