Toll-like receptor 9 antagonizes antibody affinity maturation
Open accessAbstract
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.
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TLR9 is expressed in various immune cells, such as macrophages, NK cells, B lymphocytes and plasmacytoid dendritic cells.
“Toll-like receptor 9 (TLR9) is expressed in various immune cells, such as macrophages, NK cells, B lymphocytes and plasmacytoid dendritic cells [146, 147].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [146]
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- Authors
- Akkaya, M., Akkaya, B., Kim, A. S., Miozzo, P., Sohn, H., Pena, M., Roesler, A. S., Theall, B. P., Henke, T., Kabat, J., Lu, J., Dorward, D. W., Dahlstrom, E., Skinner, J., Miller, L. H., & Pierce, S. K.
- Affiliations
- National Institute of Allergy and Infectious Diseases (US)
- National Institutes of Health (US)
- Corresponding author
- Pierce, Susan K.
- ORCID
- Venue
- Nature Immunology
- Published
- 2018-02-23
- Volume
- 19
- Issue
- 3
- Pages
- 255-266
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC5839995
- OpenAlex
- W2793820661
- Cited by
- 66
- References
- 45
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 6 · 2023: 6 · 2022: 7 · 2021: 10 · 2020: 10 · 2019: 8 · 2018: 7
- FWCI
- 3.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (UL1GM118964, TL4GM118965, RL5GM118963)
- National Institute of Allergy and Infectious Diseases (Z01AI000899)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- TLR9, affinity maturation, germinal center, B cell antigen presentation, T helper cell activation, CpG oligodeoxynucleotides, TLR9 agonist, protein vaccine, short-lived plasma cells, T cell-dependent antibody response
- MeSH terms
- Animals, Antibody Affinity, Antibody Formation, Humans, Lymphocyte Activation, Malaria Vaccines, Antigen Presentation, Germinal Center, Toll-Like Receptor 9, Mice
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