Follicular B and T cell interactions determine Brucella outcomes in an antibody-independent manner 3008

Abstract Description Brucella spp., the causative agents of brucellosis, evade adaptive immunity to establish chronic infection in humans and livestock. We have demonstrated that B cells are deleterious to Brucella control and that T follicular helper (TFH) and T follicular regulatory (TFR) responses have opposing effects on control of Brucella infection. Via sc-RNA seq, we show here that TFH and TFR affect B cell class switching during Brucella infection. However, while B cells were required for TFH and TFR to modulate resistance to infection, antibody production did not affect control of Brucella. When investigating the B cell response to brucellosis, we found that CD19 signaling in B cells promotes susceptibility to Brucella infection. In addition, via bulk and sc-RNA seq we found that Brucella infection resulted in an enhanced IFN signature in B cells. Therefore, we investigated the roles of IFN signaling in B cell responses to Brucella infection and found that STAT1, but not STAT2 signaling, was essential for B cells to promote susceptibility to Brucella. Together, these findings indicate that TFH and TFR require B cells, but not antibodies, to modulate resistance to Brucella and that B cells promote susceptibility to Brucella infection in a CD19- and STAT1-dependent manner. Funding Sources NIH R01 AI50797 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)