Analysis of immunoglobulin variable region genes from human IgG anti-DNA hybridomas.
The molecular mechanisms leading to anti-double-stranded (ds) DNA antibody production in systemic lupus erythematosus (SLE) are poorly understood. We describe here the immunoglobulin variable region genes of six human hybridomas secreting IgG anti-dsDNA antibodies derived from three SLE patients. The monoclonal IgG anti-dsDNA antibodies have been shown to be of high affinity and no multireactivity was observed (Winkler et al., Clin. Exp. Immunol., 1991. 85: 379). The comparison of the variable region genes expressed in the hybridomas with known germ-line genes as well as with the germ-line counterparts from one patient shows that the VH and VL sequences are somatically mutated. The pattern and extent of the observed somatic mutations are suggestive for an antigen-driven selection of at least four of these B cell clones. Several VH and VL genes used by the hybridomas were found to be expressed in the natural antibody repertoire, in the restricted fetal repertoire and in B cell malignancies expressing the CD5 antigen.
Winkler
T H
TH
Department of Medicine III, University Erlangen-Nürnberg, FRG.
Fehr
H
H
Kalden
J R
JR
D000595:Amino Acid Sequence; D000974:Antibodies, Antinuclear / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000276:immunology*; D005803:Genes, Immunoglobulin; D006801:Humans; D006825:Hybridomas / Q000276:immunology*; D007074:Immunoglobulin G / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation
D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D004247:DNA