Molecular characteristics of antibodies bearing an anti-DNA-associated idiotype.
Open Access
- 1 December 1991
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 174 (6) , 1639-1652
- https://doi.org/10.1084/jem.174.6.1639
Abstract
Anti-double-stranded DNA antibodies are the hallmark of the disease systemic lupus erythematosus and are believed to contribute to pathogenesis. While a large number of anti-DNA antibodies from mice with lupus-like syndromes have been characterized and their variable region genes sequenced, few human anti-DNA antibodies have been reported. We describe here the variable region gene sequences of eight antibodies produced by Epstein-Barr virus (EBV)-transformed B cells that bear the 3I idiotype, an idiotype expressed on anti-DNA antibodies and present in high titer in patients with systemic lupus. The comparison of these antibodies to the light chains of 3I+ myeloma proteins and serum antibodies reveals that EBV transformation yields B cells producing antibodies representative of the expressed antibody repertoire. The analysis of nucleotide and amino acid sequences of these antibodies suggests the first complementarity determining region of the light chain may be important in DNA binding and that paradigms previously generated to account for DNA binding require modification. The understanding of the molecular genetics of the anti-DNA response requires a more complete description of the immunoglobulin germ line repertoire, but data reported here suggest that somatic diversification is a characteristic of the anti-DNA response.Keywords
This publication has 36 references indexed in Scilit:
- Generation and analysis of clonal IgM- and IgG-producing human B cell lines expressing an anti-DNA-associated idiotype.Journal of Clinical Investigation, 1991
- Characterization of somatically mutated S107 VH11-encoded anti-DNA autoantibodies derived from autoimmune (NZB x NZW)F1 mice.The Journal of Experimental Medicine, 1991
- Antibodies elicited by pneumococcal antigens bear an anti-DNA--associated idiotype.Journal of Clinical Investigation, 1991
- The Vϰ gene repertoire in the human germ lineEuropean Journal of Immunology, 1990
- Structural characteristics of the variable regions of immunoglobulin genes encoding a pathogenic autoantibody in murine lupus.Journal of Clinical Investigation, 1990
- Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation.The Journal of Experimental Medicine, 1990
- Familial systemic lupus erythematosus. Presence of a cross-reactive idiotype in healthy family members.Journal of Clinical Investigation, 1985
- Organization and evolution of a gene cluster for human immunoglobulin variable regions of the kappa typeJournal of Molecular Biology, 1984
- Structure of the human immunoglobulin μ locus: Characterization of embryonic and rearranged J and D genesCell, 1981
- Avidity of anti-DNA antibodies in serum and IgG glomerular eluates from patients with systemic lupus erythematosus. Association of high avidity antinative DNA antibody with glomerulonephritis.Journal of Clinical Investigation, 1977