Characterization of two highly homologous autoantibody-related VH1 genes in humans.

Previously, we showed that the Humha 1lr rearranged gene was almost identical to the consensus amino acid sequence of several G6 idiotype-positive rheumatoid factor (RF) heavy chains, and to the VH gene-encoded region of the fetally expressed 51P1 cDNA. The finding led us to suggest that the ha 1lr-corresponding germline gene encodes the heavy chains of many human IgM RFs. We now report the isolation of the proposed germline gene, designated Humhv1051; it is identical to the consensus sequence of the G6 heavy chain V regions. During this experiment, we also isolated unexpectedly an additional VH1 gene, termed Humhv1051K; it differs from hv1051 by one amino acid residue. Importantly, hv1051K is identical to Humha113, the rearranged VH1 gene of a natural anti-cardiolipin antibody.