Characterization of two Human Anti-DNA Antibodies Bearing the Pathogenic Idiotype 8.12

Antibodies against double stranded DNA (dsDNA) are characteristic of systemic lupus erythematosus (SLE) and have been implicated in disease pathogenesis. Up to one third of an SLE patient's anti-dsDNA antibodies can express the lambda L chain idiotype 8.12. Serum titers of this idiotype are elevated in 50% of SLE patients, and idiotypic antibodies are present in glomerular immune deposits associated with lupus nephritis. Two EBV transformed B cell lines, KS3 from a patient with SLE and SD6 from an individual without autoimmune disease, secrete 8.12+ IgG antibodies that bind dsDNA. The 8.12+ lambda L chains of these anti-DNA antibodies are encoded by members of the V lambda II gene family; the KS3 heavy chain is encoded by a VH4-DM1-DQ52-JH6b-C gamma 1 gene rearrangement and the SD6 heavy chain is encoded by a VH3-D21/9-JH6b-C gamma 1 rearrangement. Both of these monoclonal antibodies are somatically mutated: the KS3 antibody displays mutations in complementarity determining regions (CDRs) and the SD6 antibody in framework regions (FRs). The significance of these different patterns of mutation in two potentially pathogenic anti-DNA antibodies is discussed.