PD-1 suppresses germinal center reaction and affinity maturation of antibodies 2877

Abstract Description Autoantibodies are fundamental hallmark of autoimmune diseases. Aberrant antibody production in PD-1-knockout mice has implicated PD-1 in the regulation of antibody production. We have previously reported that PD-1 stimulation using agonist antibody could suppress antibody production in immunized mice and prevent autoantibody production in lupus models. To understand the mechanism by which PD-1 stimulation downregulates antibody production, we analyzed the target cells that are responsible for this effect. Although PD-1 expression could be found in CD4+ T cells and B cells, the PD-1 agonist downregulated antibody response by targeting CD4+ T cells, but the direct effect on B cells was dispensable. This result was consistent with the inhibition of Tfh cells and germinal center B cells by PD-1 agonist treatment in vivo. The lack of germinal center formation impaired affinity maturation as shown by the reduction of high-affinity antibodies and the mutation frequency in the immunoglobulin gene. In conclusion, PD-1 negatively regulates antibody production by targeting Tfh cells and by preventing germinal center formation. The inhibition of Tfh cells and Tph cells by PD-1 agonist antibodies might provide a novel strategy for the treatment of autoimmune diseases through the reduction of autoantibody titers and their affinity to target molecules. Funding Sources Supported by Meiji Seika Pharma Co., Ltd. Topic Categories Therapeutic Approaches to Autoimmunity (THER)