Toll-like receptor 9 antagonizes antibody affinity maturation

Key events in T cell-dependent antibody responses, including affinity maturation, are dependent on the B cell’s presentation of antigen to helper T cells at critical check points in germinal center formation in secondary lymphoid organs. Here we show that Toll-like receptor 9 (TLR9) signaling blocked the ability of antigen-specific B cells to capture, process and present antigen and to activate antigen-specific helper T cells in vitro. In a mouse model in vivo and in a human clinical trial the TLR9 agonist, CpG, enhanced the magnitude of the antibody response to a protein vaccine but failed to promote affinity maturation. Thus, TLR9 signaling may enhance antibody titers at the expense of the ability of B cells to engage in germinal center events that are highly dependent on B cells’ antigen capture and presentation.