The role of B cells in the pathogenesis of rheumatoid arthritis.
The classical paradigm for rheumatoid arthritis (RA) pathogenesis holds that CD4+ T cells mediate joint damage both directly and by driving non-T effector cells to release inflammatory cytokines. By contrast, the new paradigm that is developing centers on an interaction of CD4+ T cells with B cells. Evidence reviewed in this article shows that autoreactive B cells can be driven by the T cells to produce IgG autoantibodies that may be directly involved in joint damage, and B cells are known to be critical in activating CD4+ T cells. As the B cell appears to play an important role in the RA process, it is appropriate to consider how B cell-mediated effects might be reduced or prevented in patients with this disease. As the targeted depletion of B cells with a monoclonal antibody such as rituximab appears to be clinically effective in RA patients, this approach shows great therapeutic potential.
Kotzin
Brian L
BL
Denver Autoimmunity Center of Excellence, University of Colorado Health Sciences Center, Denver, Colorado, USA. bkotzin@amgen.com
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; D001324:Autoantigens; D016207:Cytokines; D007074:Immunoglobulin G