The anti-DNA-associated idiotype 8.12 is encoded by the VλII gene family and maps to the vicinity of L chain CDR1

The 8.12 idiotype is an anti-DNA-associated Id present on λ L chains that are expressed at high titers in 50% of patients with systemic lupus erythematosus. Since this Id can be present on as much as a third of a patient's anti-DNA antibodies and is found in renal glomeruli, 8.12 is thought to be a marker for a subset of pathogenic anti-DNA autoantibodies. A molecular analysis of the 8.12 positive antibodies was designed to explore the genetic basis of this Id. Monoclonal human B cell lines were generated by transformation with EBV and λ L chain-secreting lines were analyzed for Id expression and V region gene usage. In this panel of Igλ cell lines, the 8.12 idiotype is encoded exclusively by members of the VλII gene family. The sequences of several 8.12⁺ and 8.12^- VλII genes are reported here and are used to map the 8.12 Id to the vicinity of CDR1, as well as to further characterize the large and polymorphic VλII gene family.