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 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.
Souto-Carneiro
M M
MM
Institute for Pathology, University of Wurzburg, Wurzburg, Germany.
Burkhardt
H
H
Müller
E C
EC
Hermann
R
R
Otto
A
A
Kraetsch
H G
HG
Sack
U
U
König
A
A
Heinegård
D
D
Müller-Hermelink
H K
HK
Krenn
V
V
D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000378:metabolism; D000918:Antibody Specificity / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001666:Binding Sites, Antibody; D064236:Cartilage Oligomeric Matrix Protein; D002358:Cartilage, Articular / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology* / Q000302:isolation & purification; D016326:Extracellular Matrix Proteins / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006818:Hyalin / Q000276:immunology; D006825:Hybridomas / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000097:blood; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D064235:Matrilin Proteins; D010003:Osteoarthritis / Q000097:blood / Q000276:immunology / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology / Q000302:isolation & purification; D013583:Synovial Membrane / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D064236:Cartilage Oligomeric Matrix Protein; D018985:Epitopes, B-Lymphocyte; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D064235:Matrilin Proteins; D010446:Peptide Fragments; C577553:TSP5 protein, human