Plasma cell development in synovial germinal centers in patients with rheumatoid and reactive arthritis

Plasma cells are found surrounding the inflammatory infiltrates of macropha ges, T, and B cells in the synovial tissue of patients with rheumatoid and reactive arthritis. This characteristic arrangement suggests that in the sy novial tissue CD20(+) B cells differentiate into plasma cells, To examine c lonal relationships, we have used micromanipulation to separately isolate C D20(+) B cells and plasma cells from single infiltrates. DNA was extracted, and from both populations the V-H/V-L gene repertoires was determined. The data show that in the inflamed synovial tissue activated B cells are clona lly expanded. During proliferation in the network of follicular dendritic c ells, V gene variants are generated by the hypermutation mechanism, Surpris ingly, we do not find identical rearrangements between CD20(+) B cells and plasma cells. Nevertheless, the finding of clonally related plasma cells wi thin single infiltrates suggests that these cells underwent terminal differ entiation in the synovial tissue. These results indicate that B cell differ entiation in the synovial tissue is a dynamic process. Whereas CD20(+) B ce lls may turnover rapidly, plasma cells may well be long lived and thus accu mulate 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 that take part in the local immune reaction. This will provide new i nsights into the pathogenesis of chronic inflammatory diseases like rheumat oid or reactive arthritis.