B cell regulation of CD8 T cell phenotype in vaccination and homeostasis

We have found that B cells are responsible for shaping the phenotype of naïve, effector, and memory CD8 T cells. In MD4 mice, which have a fixed BCR repertoire, we find that naïve T cells exhibit an activated/effector phenotype. This is marked by relatively high pAkt, p70-s6K, and 4e-bp1, as well as low Foxo1 and Eomes. Subunit vaccination in MD4 or B cell-depleted mice leads to a CD8 T cell response that is reduced in numbers and is effector-skewed. Additionally, adoptive transfer of CD8 T cells from C57BL/6 WT mice into MD4 mice demonstrate similar reduction in primary CD8 T cell numbers and effector phenotype upon vaccination, indicating the resulting phenotype is mostly dependent the recipient environment. In contrast, the naïve CD8 T cell development is dependent on the B cell environment where they develop, where we recovered on average 10 times more cells from a WT donor than an MD4 donor. Upon looking at memory formation in a B cell-deficient environment, there is impairment in the MD4 mice. Primary response by CD8 T cells is of the same magnitude in WT and B cell-depleted mice, but effector skewing is still prevalent with observed reductions in CD127+ memory cells. These data indicate B cells play an essential role in the establishment of not only the naïve CD8 T cells repertoire, but additionally the regulation of CD8 T cell phenotypes following subunit vaccination or infection.