Toll-like receptor 9 antagonizes antibody affinity maturation

Nat Immunol. 2018 Mar;19(3):255-266. doi: 10.1038/s41590-018-0052-z. Epub 2018 Feb 23.


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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Affinity
  • Antibody Formation / immunology*
  • Antigen Presentation / genetics*
  • Germinal Center / immunology
  • Humans
  • Lymphocyte Activation / immunology*
  • Malaria Vaccines
  • Mice
  • Toll-Like Receptor 9 / agonists
  • Toll-Like Receptor 9 / immunology*


  • Malaria Vaccines
  • Toll-Like Receptor 9