Human monoclonal rheumatoid synovial B Lymphocyte hybridoma with a new disease-related specificity for cartilage oligomeric matrix protein

Joint-specific self-Ags are considered to play an important role in the ind uction of synovial T and B cell expansion in human rheumatoid arthritis (RA ), However, the nature of these autoantigens is still enigmatic. In this st udy a somatically mutated IgG2 lambda B cell hybridoma was established from the synovial membrane of an RA patient and analyzed for its Ag specificity , A heptameric peptide of cartilage oligomeric matrix protein (COMP) could be characterized as the target structure recognized by the human synovial B cell hybridoma, The clonotypic V-H sequences of the COMP-specific hybridom a could also be detected in synovectomy material derived from five differen t RA patients but in none of the investigated osteoarthritis cases (n = 5), indicating a preferential usage of V-H genes closely related to those codi ng for a COMP-specific Ag receptor in RA synovial B cells, Moreover, the CO MP heptamer was preferentially recognized by circulating IgG in RA (n = 22) compared with osteoarthritis patients (n = 24) or age-matched healthy cont rols (n = 20; both p < 0.0001), Hence, the COMP-specific serum IgG is likel y to reflect local immune responses toward a cartilage- and tendon-restrict ed Ag that might be crucial to the induction of tissue damage in RA.