The significance of CD5+ B cells in rheumatic diseases

The presence of autoantibodies in rheumatoid arthritis (RA) and primary Sjögren' syndrome (SS) is a feature of these diseases. Because of the probable role of autoantibodies in the pathogenesis of RA and primary SS, the study of the origin and regulation of B lymphocytes producing autoantibodies is of special importance. In mice, B lymphocytes can be divided into two populations of distinct lineages, the conventional bone marrow-derived B subset and the self-renewing peripheral subset. B lymphocytes of the latter express an antigen initially described as T cell specific, the Ly-1 or CD5 antigen. In human, such CD5+B cells are found in foetal lymphoid tissue but their frequency diminishes in adult life. We have found a significant increase in CD5+B cells in the peripheral blood of patients with RA and primary SS, and a small family study of relatives of two RA patients suggests that such 'high phenotype' could be a genetic trait. Furthermore, CD5+B cells appear enriched in autoantibody-producing cells since they produce IgM-rheumatoid and other autoantibodies when suitably activated in vitro. Our current hypothesis is that persistence of high numbers of CD5+B cells in adulthood may predispose to chronic inflammatory arthritis due to the reactivity of the antigen receptor of these cells with a variety of autoantigens in the joint. Such reactivity would allow an autoimmune reactions causing the perpetuation of chronic inflammation at the disease site.