V region sequences of an idiotypically connected family of pathogenic anti-DNA autoantibodies.
The H and L chain V region sequences of nine anti-DNA mAb that are representative of a pathogenic population of autoantibodies produced by the nephritis prone (SWR x NZB)F1 (SNF1) mice, were determined. These nine anti-DNA autoantibodies were idiotypically connected members of a cross-reactive Id family called the Id564 cluster. Moreover, these autoantibodies were all cationic in charge, IgG2b in isotype, and their H chain C regions had the normal SWR parent's allotype. Although derived from two different SNF1 animals, these pathogenic autoantibodies possessed highly homologous Leader-VH sequences that could account for their idiotypic cross-reactivity. Furthermore, the VH region sequences of these anti-DNA antibodies contained numerous basic residues that could impart their cationic charge. The Leader-VH sequences of these autoantibodies were also highly homologous to that of an anti-NP antibody-related germ-line gene of C57BL/6 mice, called VH-23. Among these nine pathogenic autoantibodies, three sets of clonally related anti-DNA antibodies could be identified. Thus the Id564 cluster of cationic anti-DNA autoantibodies of SNF1 mice are encoded by highly related VH genes, and this idiotypically connected population of pathogenic autoantibodies are selected to undergo an oligoclonal expansion in the lupus-prone SNF1 mice.
O'Keefe
T L
TL
Department of Pathology, New England Medical Center, Boston, MA 02111.
Bandyopadhyay
S
S
Datta
S K
SK
Imanishi-Kari
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics*; D001483:Base Sequence; D015139:Blotting, Southern; D005803:Genes, Immunoglobulin; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007074:Immunoglobulin G / Q000235:genetics*; D007130:Immunoglobulin Idiotypes / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007526:Isoelectric Point; D051379:Mice; D008969:Molecular Sequence Data; D009393:Nephritis / Q000235:genetics / Q000276:immunology
D000974:Antibodies, Antinuclear; D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region