Structure and function of anti-DNA autoantibodies derived from a single autoimmune mouse

Four monoclonal anti-DNA antibodies derived from a single autoimmune MRL/lpr mouse were studied. Three of these antibodies showed similarities in DNA binding; the fourth had a much higher specific activity for single-stranded DNA and, in addition, was unique in binding double-stranded DNA and cardiolipin. Complete nucleotide sequences of heavy- and light-chain variable regions demonstrated that all four antibodies are clonally related. The sequences also showed numerous somatic mutations, the distribution of which suggests that positive selection by antigen operated on these clonally related autoantibodies.