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 mu heavy chain clones of the VH4 family identified in the synovial tissue from the BD patient, 8 clones showed identical nucleotide sequences, and therefore, 18.2% were clonally expanded. For y heavy chain, 4 of 50 clones of the VH3 family showed nearly identical sequences; therefore, 4-8% were clonally expanded. The kappa 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.