A Breach in Tolerance: The Roles of B Cells in the Immunopathogenesis of Rheumatoid Arthritis.

Abstract

Rheumatoid arthritis (RA) represents the most common chronic inflammatory joint disease, and is still a major medical challenge because of unresolved issues related to both etiologic and patheogenetic questions. B cells have historically been considered as not preferentially involved in the immunopathogenesis of infammatory joint disease, in particular RA. However, B lymphocytes do play critical rols in the pathogenesis of rheumatoid arthritis. B cells are the source of rheumatoid factors and anti-citrullinated protein antibodies, which contribute to immune complex formation and citrullinated protein antibodies, which contrib ute3 to immune complex formation and complement activiation in the joints. B cells are not just restricted to autoantibody formation. They have the capacity to promote T cell activation. Antigen-specific B cells are indispensable as antigen presenting cells for the actvation autoreactive T cells. B cels both respond to and produce the chemokines and cytokines that promote leukocyte infiltration into the joints, formation of ectopic lymphoid structures, angiogenesis and synovial hyerplasia. Based on the evidence supporting B cell involvement in the pathophysiology of autoimmune disease, B cell targeted therapies, like anti-CD20 monoclonal antibody, Rituximab, currently provide therapeutic benefit to many patients suffering from RA. This review article will discuss the roles of B cells in RA, and provide some insight into the beneficial application of B cell directed therapy.