Variable Region Sequence Analysis of Anti-DNA Antibodies: Evidence for a Family of Closely Related Germ-Line V H Genes Encoding Lupus Autoantibodies

Cloning and sequencing of the V regions of the anti-DNA monoclonal antibodies (mAbs), H438 and H130, indicate that H438 is encoded by a J558 V_H gene, a single D region nucleotide, and unmutated J_H1, V_x-1C and J_x1 genes, and the H130 L chain is encoded by a V_x-21 subgroup gene and J_x1 gene. Identification of V_H438, which shared V_H hybridization pattern with 6% of a panel of 352 MRL/lpr hybridomas, suggests that the frequency of J558 use among spontaneously activated B cells in MRL/1pr mice is greater than previously reported. The V_HH438 J558 family gene is identical to V_HPAR, which encodes the independently derived MRL/lpr autoantibody, MRP-2, and is highly homologous to the previously reported V_HH130, which is identical to a BALB/c germ-line V_H gene. Comparison of consensus sequences of homologous autoantibodies and previously reported restriction mapping suggest that a minimum of three highly related J558 germ-line genes encode lupus autoantibodies.