Journal Article

Toll-like receptor 9 antagonizes antibody affinity maturation

Kabat, Juraj, Miller, Louis H., Pierce, Susan K., Akkaya, Munir, Lu, Jinghua, Pena, Mirna, Miozzo, Pietro, Henke, Travis, Kim, Ann S., Dorward, David W., Dahlstrom, Eric, Akkaya, Billur, Roesler, Alexander S., Skinner, Jeff, Sohn, Haewon, Theall, Brandon P.

2018

Overview

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 checkpoints in germinal-center formation in secondary lymphoid organs. Here we found that signaling via Toll-like receptor 9 (TLR9) 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 might 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’ capture and presentation of antigen. The presentation of antigen by germinal-center B cells to follicular T cells engenders the process of antibody affinity maturation and humoral memory. Pierce and colleagues show that TLR9 signaling in B cells antagonizes B cell–mediated antigen presentation, which leads to the enhanced generation of short-lived plasma cells and the production of lower-affinity antibodies.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Affinity / Animals / Antibodies / Antibody Affinity / Antibody Formation - immunology / Antibody response / Antigen presentation / Antigen Presentation - genetics / Antigens / B cells / Biomedical and Life Sciences / Biomedicine / Clinical trials / Germinal Center - immunology / Humans / Immunology / Infectious Diseases / Lymphocyte Activation - immunology / Lymphocytes B / Lymphocytes T / Malaria Vaccines / Mice / T cell receptors / T cells / TLR9 protein / Toll-Like Receptor 9 - agonists / Toll-Like Receptor 9 - immunology / Toll-like receptors / Vaccines