The B cell repertoire of patients with rheumatoid arthritis. II. Increased frequencies of IgG+ and IgA+ B cells specific for mycobacterial heat-shock protein 60 or human type II collagen in synovial fluid and tissue

Objective. A qualitative and quantitative analysis of the functional, antigen-specific B cell receptor repertoire of patients with rheumatoid arthritis (RA) in synovial and peripheral compartments. Methods. B cells were activated to grow and differentiate at high efficiency in vitro under limiting-dilution conditions. Isotype and specificity of the secreted Ig were tested by enzyme-linked immunosorbent assay. Results. In contrast to peripheral B cells, most synovial B cells had already switched to IgG/IgA in vivo. The frequencies of B cells specifically recognizing foreign antigens were decreased within the synovial population, whereas the frequencies of B cells specific for type II collagen, mycobacterial heat-shock protein 60 (hsp60), or IgG Fc fragments were significantly increased, revealing a negative correlation in terms of frequencies. Conclusion. B cells specific for human type II collagen, hsp60, and IgG Fc fragments are produced and/or expanded locally within the affected joints of RA patients. Thus, the specific immune system is definitely involved in the local inflammatory and destructive processes.