Regulation of anti-Sm autoantibodies by the immunoglobulin heavy chain locus.
Anti-Sm antibodies are specific markers for systemic lupus erythematosus in MRL mice and in humans. The prevalence of anti-Sm positivity in inbred MRL/Mp-lpr/lpr(MRL/lpr) mice is consistently about 25% at 5 mo of age, when the disease is at its peak. The control of the development of anti-Sm in individual MRL/lpr mice has been shown to be the result of stochastic factors, and previous research has indicated that the immunoglobulin heavy chain (IgH) b allotype may be more amenable to the production of anti-Sm. We have now further investigated the influence of the IgH genetic locus on the production of anti-Sm and other autoantibodies in an allotype congenic MRL strain, the MRL/Mp-Ipr/Ipr-IgHb (MRL/lpr-IgHb). Strikingly, 78% of MRL/lpr-IgHb mice produced anti-Sm, compared with 27% of contemporaneous MRL/lpr (IgHj) mice. Of those mice that were positive for anti-Sm, the MRL/lpr-IgHb strain produced significantly higher levels of anti-Sm than did the anti-Sm positive MRL/lpr mice. No differences were observed between the conventional MRL/lpr and the MRL/lpr-IgHb levels of antichromatin, anti-ssDNA, antiribosomal P, or anti-Su. In addition, kidney function, which was assessed by measuring serum urea nitrogen levels, was similar in the two strains. These results support the notion that the control of anti-Sm production in MRL/lpr mice operates through the IgH locus.
Halpern
M D
MD
Department of Microbiology/Immunology, University of North Carolina, Chapel Hill 27599.
Craven
S Y
SY
Cohen
P L
PL
Eisenberg
R A
RA
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001324:Autoantigens; D015415:Biomarkers; D001806:Blood Urea Nitrogen; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007668:Kidney / Q000503:physiopathology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012261:Ribonucleoproteins / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins
D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D007143:Immunoglobulin Heavy Chains; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins