Regulation of anti-Sm autoantibodies by the immunoglobulin heavy chain locus

• Published in: The Journal of immunology (1950) Vol. 151; no. 12; pp. 7268 - 7272
• Main Authors: Halpern, MD, Craven, SY, Cohen, PL, Eisenberg, RA
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.12.1993; American Association of Immunologists
• Subjects: Animals; Autoantibodies - biosynthesis; Autoantigens; Biological and medical sciences; Biomarkers; Blood Urea Nitrogen; Genes, Immunoglobulin; Humans; Immunoglobulin Heavy Chains - genetics; Immunopathology; Immunotherapy (general aspects); Kidney - physiopathology; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - physiopathology; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Ribonucleoproteins - immunology; Ribonucleoproteins, Small Nuclear; snRNP Core Proteins; Autoimmunity; Immunopathology; Animal model; Heavy peptide chain; Immunoglobulins; Ribonucleoprotein; Genetic inheritance; Rodentia; Autoantibody; Immune regulation; Vertebrata; Specificity; Mammalia; Mouse; Locus
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.151.12.7268

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.