VARIABLE REGION SEQUENCE-ANALYSIS OF ANTI-DNA ANTIBODIES - EVIDENCE FOR A FAMILY OF CLOSELY RELATED GERM-LINE VH 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(H)1, V(kappa)-1C and J(kappa)1 genes, and the H130 L chain is encoded by a V(kappa)-21 subgroup gene and J(kappa)l gene. Identification of V(H)438, 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(H)H438 J558 family gene is identiCal to V(H)PAR, which encodes the independently derived MRL/1pr autoantibody, MRP-2, and is highly homologous to the previously reported V(H)H130, 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.