An Agonistic Anti-CD137 Antibody Disrupts Lymphoid Follicle Structure and T-Cell-Dependent Antibody Responses

Cell Rep Med. 2020 Jun 23;1(3):100035. doi: 10.1016/j.xcrm.2020.100035.


CD137 is a costimulatory receptor expressed on natural killer cells, T cells, and subsets of dendritic cells. An agonistic monoclonal antibody (mAb) against CD137 has been used to reduce tumor burden or reverse autoimmunity in animal models and clinical trials. Here, we show that mice treated with an agonistic anti-CD137 mAb have reduced numbers of germinal center (GC) B cells and follicular dendritic cells (FDCs) in lymphoid tissues, which impair antibody responses to multiple T-cell-dependent antigens, including infectious virus, viral proteins, and conjugated haptens. These effects are not due to enhanced apoptosis or impaired proliferation of B cells but instead correlate with changes in lymphoid follicle structure and GC B cell dispersal and are mediated by CD137 signaling in CD4+ and CD8+ T cells. Our experiments in mice suggest that agonistic anti-CD137 mAbs used in cancer and autoimmunity therapy may impair long-term antibody and B cell memory responses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibody Formation / immunology
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Cell Proliferation / physiology
  • Dendritic Cells, Follicular / immunology*
  • Germinal Center / immunology
  • Killer Cells, Natural / immunology
  • Lymphoid Tissue / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / immunology*


  • Antibodies, Monoclonal
  • Tumor Necrosis Factor Receptor Superfamily, Member 9