Cutting edge: anti-tumor necrosis factor therapy in rheumatoid arthritis inhibits memory B lymphocytes via effects on lymphoid germinal centers and follicular dendritic cell networks

J Immunol. 2008 Jan 15;180(2):688-92. doi: 10.4049/jimmunol.180.2.688.


Rheumatoid arthritis (RA) is mediated by a proinflammatory cytokine network with TNF at its apex. Accordingly, drugs that block TNF have demonstrated significant efficacy in the treatment of RA. A great deal of experimental evidence also strongly implicates B cells in the pathogenesis of RA. Yet, it remains unclear whether these two important players and the therapies that target them are mechanistically linked. In this study we demonstrate that RA patients on anti-TNF (etanercept) display a paucity of follicular dendritic cell networks and germinal center (GC) structures accompanied by a reduction in CD38+ GC B cells and peripheral blood memory B cell lymphopenia compared with healthy controls and RA patients on methotrexate. This study provides initial evidence in humans to support the notion that anti-TNF treatment disrupts GC reactions at least in part via effects on follicular dendritic cells.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • B-Lymphocytes / drug effects*
  • Dendritic Cells, Follicular / drug effects
  • Dendritic Cells, Follicular / immunology
  • Etanercept
  • Female
  • Germinal Center / drug effects
  • Germinal Center / immunology
  • Germinal Center / pathology
  • Humans
  • Immunoglobulin G / pharmacology
  • Immunoglobulin G / therapeutic use*
  • Immunologic Memory / drug effects*
  • Male
  • Middle Aged
  • Palatine Tonsil / immunology
  • Palatine Tonsil / pathology
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Etanercept