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

• Published in: The Journal of immunology (1950) 2001-03, Vol.166 (6), p.4202-4208
• Main Authors: Souto-Carneiro, Maria M, Burkhardt, Harald, Muller, Ewa C, Hermann, Ralph, Otto, Albrecht, Kraetsch, Hans-Georg, Sack, Ulrich, Konig, Achim, Heinegard, Dick, Muller-Hermelink, Hans Konrad, Krenn, Veit
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - biosynthesis; Antibodies, Monoclonal - blood; Antibodies, Monoclonal - genetics; Antibodies, Monoclonal - metabolism; Antibody Specificity - genetics; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - pathology; Autoantibodies - blood; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B-Lymphocytes - pathology; Binding Sites, Antibody; Cartilage Oligomeric Matrix Protein; Cartilage, Articular - immunology; COMP protein; Epitopes, B-Lymphocyte - immunology; Epitopes, B-Lymphocyte - isolation & purification; Extracellular Matrix Proteins - immunology; Extracellular Matrix Proteins - metabolism; Gene Expression Regulation - immunology; Glycoproteins - immunology; Glycoproteins - metabolism; Humans; Hyalin - immunology; Hybridomas - immunology; Hybridomas - metabolism; Hybridomas - pathology; Immunoblotting; Immunoglobulin G - blood; Immunoglobulin Heavy Chains - biosynthesis; Immunoglobulin Heavy Chains - genetics; Matrilin Proteins; Osteoarthritis - blood; Osteoarthritis - immunology; Osteoarthritis - pathology; Peptide Fragments - immunology; Peptide Fragments - isolation & purification; Synovial Membrane - immunology; Synovial Membrane - metabolism; Synovial Membrane - pathology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.6.4202

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.