Oligoclonal B lymphocyte expansion in the synovium of a patient with Behçet's disease

Objective. Plasma cell infiltration is observed in recurrent arthritis associated with Behçet's disease (BD). The immune mechanism underlying B lymphocyte proliferation in the synovium is unclear. One hypothesis involves nonspecific polyclonal activation and another involves antigen-driven activation. The present study was undertaken to test both hypotheses and identify immunoglobulin genes that are clonally expanded in the synovium. Methods. Peripheral blood lymphocytes (PBL) and synovial cells from a patient with BD and PBL from a healthy control subject were obtained. Complementarity-determining region 3 (CDR3) fingerprinting analysis and nucleotide sequence analysis of Ig transcripts derived from clonally expanded B lymphocytes were performed in parallel. Results. Of 44 μ heavy chain clones of the V_H4 family identified in the synovial tissue from the BD patient, 8 clones showed identical nucleotide sequences, and therefore, 18.2% were clonally expanded. For γ heavy chain, 4 of 50 clones of the V_H3 family showed nearly identical sequences; therefore, 4-8% were clonally expanded. The κ light chain did not show a dominant band, but a clone with a 12-amino acid CDR3 showed 3% clonal expansion. Somatic mutations were frequently observed, with a high ratio of replacement to silent mutations in the CDRs compared with the framework regions. Three Ig genes expressed in the clonally expanded B lymphocytes were derived from germline gene segments reported to be involved in the production of autoantibodies. Conclusion. These results support the hypothesis that antigen-driven clonal B lymphocyte proliferation occurs in the synovium in BD. Immunoglobulin transcripts clonally expanded in the synovium were identified.