Characterization of somatically mutated S107 VH11-encoded anti-DNA autoantibodies derived from autoimmune (NZB x NZW)F1 mice.
We have studied 19 S107 heavy chain variable region gene (VH11)-encoded monoclonal antibodies from NZBWF1 mice. These studies show that a single VH gene can encode both antibodies to foreign antigens (anti-phosphorylcholine) and to self antigens (anti-double-stranded DNA) in the same animal. All of the anti-DNA antibodies contain many somatic mutations compared with the relevant germline genes. Since the anti-DNA antibodies were extensively somatically mutated and had undergone isotype switching, the response seems to be T cell dependent. While some of the antibodies appear to be the products of an antigen-driven and antigen-selected response, a number of characteristics of the antibodies suggest that forces other than antigen are contributing to the stimulation and selection of this response.
Behar
S M
SM
Department of Cell Biology, Irvington House Institute, Albert Einstein College of Medicine, Bronx, New York 10461.
Lustgarten
D L
DL
Corbet
S
S
Scharff
M D
MD
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics*; D001483:Base Sequence; D004247:DNA / Q000276:immunology*; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D015345:Oligonucleotide Probes; D011485:Protein Binding
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D015345:Oligonucleotide Probes; D004247:DNA