Molecular analysis of the murine lupus-associated anti-self response: involvement of a large number of heavy and light chain variable region genes

• Published in: European journal of immunology Vol. 17; no. 1; p. 91
• Main Authors: Kofler, R, Noonan, D J, Strohal, R, Balderas, R S, Møller, N P, Dixon, F J, Theofilopoulos, A N
• Format: Journal Article
• Language: English
• Published: Germany 01.01.1987
• Subjects: Animals; Antibodies, Monoclonal - genetics; Autoantibodies - genetics; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; Base Sequence; Disease Models, Animal - genetics; Disease Models, Animal - immunology; Female; Gene Expression Regulation; Genes; Histones - immunology; Hybridomas - analysis; Immunoglobulin G - genetics; Immunoglobulin Heavy Chains - genetics; Immunoglobulin kappa-Chains - genetics; Immunoglobulin Light Chains - genetics; Immunoglobulin M - genetics; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Mice; Mice, Inbred Strains - genetics; Mice, Mutant Strains - genetics; Mice, Mutant Strains - immunology; Rheumatoid Factor - genetics; RNA, Messenger - analysis; Sequence Homology, Nucleic Acid
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.1830170116

The mRNA encoding heavy and light chains of a hybridoma-derived monoclonal IgM, kappa anti-immunoglobulin (rheumatoid factor) and an IgG3, kappa anti-histone autoantibody from systemic lupus erythematosus and arthritis-prone MRL/Mp-lpr/lpr mice have been molecularly cloned, and the nucleotide sequences corresponding to their variable regions have been determined. To investigate whether autoantibodies with specificities frequently observed in lupus disease might share common structural components, the sequences obtained in this study have been compared with those of a monoclonal MRL/Mp-lpr/lpr IgM, kappa anti-DNA autoantibody previously analyzed in our laboratory (J. Exp. Med. 1985. 161: 805). The 3 immunoglobulins employed different heavy chain variable region (VH) genes belonging to the large J588 VH gene family, kappa light chain variable region (V kappa) genes from 3 different V kappa groups, and different diversity and joining segments. Our findings suggest that murine lupus-associated autoantibodies of different specificities do not have genetic components in common to signal their self-reactive nature and are encoded by a large number of immunoglobulin gene elements.