Human Monoclonal Rheumatoid Synovial B Lymphocyte Hybridoma with a New Disease-Related Specificity for Cartilage Oligomeric Matrix Protein

Abstract

Joint-specific self-Ags are considered to play an important role in the induction of synovial T and B cell expansion in human rheumatoid arthritis (RA). However, the nature of these autoantigens is still enigmatic. In this study 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 hybridoma could also be detected in synovectomy material derived from five different RA patients but in none of the investigated osteoarthritis cases (n = 5), indicating a preferential usage of V(H) genes closely related to those coding for a COMP-specific Ag receptor in RA synovial B cells. Moreover, the COMP heptamer was preferentially recognized by circulating IgG in RA (n = 22) compared with osteoarthritis patients (n = 24) or age-matched healthy controls (n = 20; both p < 0.0001). Hence, the COMP-specific serum IgG is likely to reflect local immune responses toward a cartilage- and tendon-restricted Ag that might be crucial to the induction of tissue damage in RA.