IgG anti-DNA autoantibodies within an individual autoimmune mouse are the products of clonal selection.
Although mice from almost all inbred strains produce IgM anti-DNA antibody in response to B cell mitogens, only (NZB x NZW)F1 mice and mice from other strains that are genetically predisposed to autoimmunity spontaneously produce anti-DNA antibody of the IgG isotype. Because (NZB x NZW)F1 mice display marked B cell hyperactivity, anti-DNA antibody production in these mice has been thought to result from spontaneous, polyclonal B cell activation. Although this may be true for IgM anti-DNA antibodies, our results demonstrate that IgG anti-DNA antibodies are not polyclonal. Rather, IgG anti-DNA autoantibodies within an individual autoimmune mouse are oligoclonal and somatically mutated. These results demonstrate that IgG anti-DNA autoantibodies are the products of clonally selective B cell stimulation and exhibit the same characteristics as secondary immune antibodies to conventional immunogens: they are IgG, they are clonally restricted, and they are somatically mutated.
Marion
T N
TN
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510.
Bothwell
A L
AL
Briles
D E
DE
Janeway
C A
CA
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000235:genetics; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D015139:Blotting, Southern; D002999:Clone Cells / Q000378:metabolism*; D003433:Crosses, Genetic; D004247:DNA / Q000276:immunology* / Q000302:isolation & purification; D015321:Gene Rearrangement; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D007130:Immunoglobulin Idiotypes / Q000096:biosynthesis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D004247:DNA