Evidence for an antigen-driven immune response in the chronically inflamed synovium

Recently it has been shown that proinflammatory cytokines, like TNF-alpha and lymphotoxin play a crucial role in the organogenesis of the lymphoid tissue. Thus, during chronic inflammation, in the affected tissue, these cytokines may promote the development of a micro-environment which supports a local immune response. In patients with rheumatoid arthritis large lymphocytic infiltrates are often seen in the synovial tissue. These cell clusters have a characteristic arrangement of T, B and plasma cells. Proliferating B cells are found only centrally in a network of follicular dendritic cells. Using micro-manipulation CD20⁺ B cells and plasma cells were isolated separately from different parts of single infiltrates. DNA was extracted and the V_H/V_L gene repertoires determined. The data show that within the network of follicular dendritic cells there is an oligoclonal expansion of B cells. During proliferation V-gene variants are generated by the hypermutation mechanism. The pattern of somatic mutations suggests that both naive and memory B cells become activated in the synovial tissue. Within single infiltrates we did not find identical rearrangements between CD20⁺ B and plasma cells. Nevertheless, the finding of clonally related plasma cells suggests that these cells underwent terminal differentiation in the synovial tissue. The analysis of individual B cells recovered from synovial tissue opens a new way to determine the specificity of those cells which take part in the local immune reaction.