Utilization of the VH4-21 gene segment by anti-DNA antibodies from patients with systemic lupus erythematosus

FK Stevenson, C Longhurst, CJ Chapman… - Journal of …, 1993 - Elsevier
FK Stevenson, C Longhurst, CJ Chapman, M Ehrenstein, MB Spellerberg, TJ Hamblin…
Journal of autoimmunity, 1993Elsevier
Abstract A monoclonal antibody (9G4) which detects an idiotape (Id) rising from heavy
chains encoded by the VH 4-21 gene segment has been utilized to investigate the role of
this gene in encoding anti-DNA antibodies in SLE. Two hybridomas secreting Id-positive anti-
DNA antibodies were established from two patients with SLE, with one (RT-79) an IgMκ and
the other (D-5) IgGκ. Nucleotide sequence analysis of the heavy chain variable regions
revealed involvement of the VH 4-21 gene; the IgM antibody used the gene in germ line …
Abstract
A monoclonal antibody (9G4) which detects an idiotape (Id) rising from heavy chains encoded by the VH4-21 gene segment has been utilized to investigate the role of this gene in encoding anti-DNA antibodies in SLE. Two hybridomas secreting Id-positive anti-DNA antibodies were established from two patients with SLE, with one (RT-79) an IgMκ and the other (D-5) IgGκ. Nucleotide sequence analysis of the heavy chain variable regions revealed involvement of the VH4-21 gene; the IgM antibody used the gene in germ line configuration, whereas the IgG antibody had 18 nucleotide changes. The CDR3 sequences for both the antibodies had a predominance of basic amino acids, with RT-79 having five and D-5 two arginine residues respectively. The VH4-21 gene segment, often in germ line configuration, is also used by IgM autoantibodies against red cell Ii antigens. However, IgM from a panel of six hybridomas secreting antibodies of Ii specificity, had no detectable activity against DNA. Conversely, RT-79 had only a weak ability to agglutinate red cells. Comparisons of Ig variable regions indicate that the amino acids in the CDR3 region of the μ chain influence the ability of IgM encoded by the VH4-21 gene segment to discriminate between a carbohydrate Ii antigen and DNA, and strongly support the suggested role of arginine in interaction with DNA. Sera from patients with SLE were found to have significantly raised levels of Id which was expressed by anti-DNA antibodies against both ss and dsDNA.
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