Genetic association between natural autoantibody responses to histones and DNA in murine lupus.
Genetic regulation of the spontaneous anti-histone antibody production in systemic lupus erythematosus (SLE) was studied using the H-2-congenic and T cell receptor beta chain gene complex (TCR beta)-congenic NZB and NZW strains and their crosses. We found that the original, parental H-2d/d NZB mice produced significantly higher titers of serum IgM class anti-histone antibodies than did the congenic H-2d/z or H-2z/z NZB mice. However, none of these three NZB strains produced IgG antibodies. The NZW strain of any H-2 haplotype did not produce IgM and IgG anti-histone antibodies. The IgG anti-histone antibodies were produced only by H-2d/z heterozygous NZB x NZW F1, but not by homozygous H-2z/z or H-2d/d NZB x NZW F1 mice. In studies using (NZB x NZW) F1 x NZB backcross mice, only the progeny having both H-2d/z and NZW-type TCR beta genotypes produced high amounts of IgG antibodies. There was a tight linkage between the NZW-type TCR beta and the production of IgG anti-histone antibodies in TCR beta-congenic NZB x NZW F1 mice. All these findings were in keeping with our preceding observations on the genetic regulation of anti-DNA antibodies in these mice and suggest that certain common mechanisms such as super-antigen-mediated or common idiotope-mediated regulations may underlie the production of these two distinct autoantibodies in NZB x NZW F1 mice.
Tokushige
K
K
Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.
Kinoshita
K
K
Hirose
S
S
Shirai
T
T
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000096:biosynthesis*; D004247:DNA / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics; D006239:Haplotypes; D006657:Histones / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008814:Mice, Inbred NZB; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D006183:H-2 Antigens; D006657:Histones; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA