Molecular heterogeneity of auto-anti-idiotypic antibodies in MLR-lpr/lpr mice.
The VH and V kappa gene families expressed by 20 monoclonal auto-anti-idiotypes (Ab2) derived from unmanipulated MLR-lpr/lpr mice were determined by Northern blotting. Complete variable region sequences of six Ab2, along with three additional V kappa-JH Ab2 sequences, were obtained. These auto-anti-idiotypes arose spontaneously in the animals, and they bound specifically to an idiotypic determinant (Id/r) on mAb 28/12, a monoclonal IgG2b MLR-lpr/lpr anti-small nuclear ribonucleoprotein antibody. The 16 Ab2 heavy chains belonged to 7 different VH gene families, and the 10 Ab2 light chains were derived from 8 V kappa families. The light chains of two Ab2 were approximately 99% identical; the remaining variable region sequences were highly heterogeneous. There was no correlation between primary amino acid sequence of either heavy or light chain and idiotypic properties of the auto-anti-idiotypes. Six Ab2 used VH or V kappa genes that are identical to known germ-line genes. A high proportion of the spontaneous auto-anti-idiotypes was shown to have autoantibody activity (anti-DNA, anti-ribonucleoprotein), or specific binding reactions with lipopolysaccharide of Salmonella RE, or both properties. The structural diversity of spontaneous MLR-lpr/lpr auto-anti-idiotypes differs sharply from the structural homogeneity reported for Ab2 induced in normal animals against syngeneic Ab1. Our results suggest that auto-anti-idiotypes might arise independently of an immunogenic stimulus from an Ab1.
Koizumi
T
T
Department of Medicine, New England Medical Center, Tufts University School of Medicine, Boston, MA 02111.
Puccetti
A
A
Migliorini
P
P
Barrett
K J
KJ
Schwartz
R S
RS
D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000235:genetics*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000235:genetics*; D001483:Base Sequence; D001667:Binding, Competitive; D003429:Cross Reactions; D006825:Hybridomas; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology*; D008969:Molecular Sequence Data; D012689:Sequence Homology, Nucleic Acid
D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region