Brucellosis, caused by intracellular pathogens of the Brucella genus, often results in chronic and/or lifelong infection. While T cells can contribute to control of Brucella, this typically does not result in sterile immunity, and the mechanisms underlying the inability of T cells to clear infection remain unclear. We previously found that B cells promote susceptibility to Brucella in a CD4+ T cell dependent manner. Here we report that B cell MHCII expression enhances susceptibility to infection, and investigated the role of B cell antigen specificity and presentation in this process. We found that B cell receptor specificity facilitates enhanced susceptibility to infection as well as Brucella entry into B cells in vivo. Investigation of the role of individual B cell subsets demonstrated that follicular B cells can inhibit protective CD4+ T cell responses. Evaluation of CD4+ T cell populations revealed that B lymphocytes promote FoxP3 expression preferentially amongst T follicular cell populations following Brucella infection. Additionally, CD40L blockade enhances protection against Brucella in a B cell dependent manner concomitant with a decrease in T follicular regulatory cells (TFR). Interestingly, PD-1 blockade resulted in an increase in TFR populations as well as an increased susceptibility to Brucella infection in a B and CD4+ T cell-dependent manner. Together, these data suggest B and CD4+ T cell interactions within the follicle promote TFR cell populations which in turn could promote susceptibility to Brucella infection. Supported by NIH Grant:1R21AI135160 NIH Grant:1R01AI150797