B cells shape näive and vaccine-elicited CD8 T cell phenotype and fate decisions 2073

Abstract Description Despite long held beliefs that B cells and CD8 T cells act independently, our recent investigations demonstrate that B cells are responsible for shaping the phenotype and fate decisions of naïve and effector CD8 T cells. Following vaccination or infection, antigen-specific CD8 T cells are skewed toward terminal differentiation in B cell-deficient mice and in MD4 mice, which have a fixed BCR repertoire, as compared to WT controls. The result is significantly fewer CD127high memory-fated CD8 T cells and defective long-term memory. This phenotype is recapitulated upon B cell depletion using CD19-cre x iDTR mice or using anti-CD19 CAR T cells in WT mice, and in the context of multiple vaccine strategies and infections. Because these data indicated that the presence or absence of B cells leaves an imprint on naïve T cells, we looked for evidence of differential programming prior to activation. Flow cytometry analysis of naïve CD8 T cells isolated from the periphery of both MD4 mice and human populations depleted of B cells revealed an effector-skewing with decreases in FOXO1 and CD127, and corresponding increases in Granzyme A and other proteins associated with terminal differentiation. Overall, these data indicate B cells play an essential role in the establishment of not only the naïve CD8 T cell repertoire, but they also influence the CD8 T cell response following vaccination or infection. Funding Sources NIH grants AI066121, AI148919, and AI126899 Topic Categories Vaccines and Immunotherapy (VAC)