Lack of B Lymphocytes Enhances CD8 T Cell-Mediated Resistance against Respiratory Viral Infection but Compromises Memory Cell Formation.

Following a respiratory virus infection, CXCR3 CX3CR1 and CXCR3 CX3CR1 CD8 T cells localize to different compartments within the lung and play an important role in host resistance, but mechanisms governing their optimal generation are poorly defined. We serendipitously found that B cell-deficient (μMT) mice were highly resistant to lethal infection with a virulent poxvirus strain and that depletion of CD8 T cells rendered these mice susceptible to infection. B cells were not required for the expansion of virus-specific CD8 T cells, but a greater proportion of activated CD8 T cells acquired an effector-like CXCR3 CX3CR1 phenotype in the absence of B cells. After recovery from infection, CD8 T cells in μMT mice contracted normally but failed to survive and seed the memory cell pool in both the lungs and spleen. These findings reveal a previously unappreciated role for B cells in regulating the balance between CD8 T cell-mediated resistance against respiratory viral infection and memory cell development. B cells play critical role in host resistance against many respiratory viral infections. However, the role of B cells beyond antibody-producing cells is less well defined. In this study, we made a surprising observation that mice lacking B cells were more resistant to respiratory infection with vaccinia virus than wild-type mice. This enhanced resistance was mediated by CD8 T cells because when we depleted CD8 T cells in B cell-deficient mice, these mice were unable to survive the infection. Interestingly, CD8 T cells in B cell-deficient mice were skewed more toward effector phenotype and less toward memory phenotype, which resulted in severely compromised memory CD8 T cell development. Thus, our study shows a novel role of B cells as regulators of CD8 T cell-mediated host resistance and memory CD8 T cell formation during respiratory viral infection.