Qualities of Tumor Antigen and Signals From CD4+ T cells Shape Germinal Center and Extrafollicular B cell Responses to Unlock Key Mechanisms of Anti-Tumor Immunity 4200

Abstract Description B cells predict survival and treatment success in many cancers. Yet, gaps in identified mechanisms that regulate B cell function in cancer limit therapeutic utilization. In our studies of B cell responses to aggressive mouse tumors, we find that antigen and signals from CD4+ T cells to B cells controls the timing, composition, and anti-tumor function in B cell responses to tumors. By tracking model antigen and antigen-specific B cells in tumor draining lymph nodes, we demonstrate that neoantigen solubility or being membrane bound along with the degree of BCR-antigen affinity shapes B cell mediated tumor control, extrafollicular and germinal center activity, and the capacity for B cells to expand antigen targeting. We further show that in response to antigen, B cells and T cells engage in co-activation while IL21 and CD40Lg signals from CD4+ T cells shape B cell responses to antigen by influencing extrafollicular and germinal center activity, class-switching, and memory B cell and plasma cell responses. Further, we find CD40 ligand and neoantigen elicits extrafollicular memory B cells that use CD86 signals to cause CD8+ T cells to become cytotoxic and mediate tumor control. Together, these findings advance the understanding of how B cells are regulated and function to provide durable anti-tumor immune responses. Funding Sources DPH is supported by Susan G Komen, Metavivor, Curebound, the California Breast Cancer Research Program, and funding from the Salk Institute by an NIH P30. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)