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 VH gene, a single D region nucleotide, and unmutated JH1, V kappa-1C and J kappa 1 genes, and the H130 L chain is encoded by a V kappa-21 subgroup gene J kappa 1 gene. Identification of VH438, which shared VH 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/lpr mice is greater than previously reported. The VHH438 J558 family gene is identical to VHPAR, which encodes the independently derived MRL/lpr autoantibody, MRP-2, and is highly homologous to the previously reported VHH130, which is identical to a BALB/c germ-line VH 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.
Foster
M H
MH
Department of Medicine, University of Pennsylvania, Philadelphia 19104.
Madaio
M P
MP
Barrett
K J
KJ
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D004247:DNA / Q000276:immunology*; D005854:Germ Cells; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008177:Lupus Vulgaris / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D012689:Sequence Homology, Nucleic Acid
D001323:Autoantibodies; D007135:Immunoglobulin Variable Region; D004247:DNA