Resistance to tolerance induction is not prerequisite to development of murine SLE.
Four different SLE-prone mice, NZB, (NZB x NZW)F1, MRL/MpJ-lpr/lpr, and male BXSB/MpJ, resisted the induction of tolerance to human IgG (HGG) at 5 wk, but not before 3 wk of age. However, female F1 hybrids between NZW and BXSB mice were easily made tolerant to HGG, although they develop an acute form of typical SLE similar to that seen in (NZB x NZW)F1 hybrid females. In addition, C57BL/6 mice bearing a mutant gene, lpr (lymphoproliferation), which produced significant amounts of various autoantibodies characteristic of murine SLE, were still as susceptible to tolerance induction as control C57BL/6 mice. In contrast, both (NZW x BXSB)F1 and (C3H x BXSB)F1 hybrid males carrying the abnormal Y chromosome of BXSB mice failed to become tolerant to HGG, although the extent of resistance to tolerance induction was less significant in (C3H x BXSB)F1 males than in (NZW x BXSB)F1 males. Our results suggest that 1) the defect in tolerance induction to heterologous IgG such as HGG is not necessarily required for the development of an SLE-like syndrome in mice; 2) the induction or enhanced production of autoantibodies by the lpr gene is not related to this cellular abnormality; but 3) a Y chromosome-associated factor from BXSB mice plays a significant role in the abnormality to resist tolerance induction as well as the acceleration of SLE. Our observations are consistent with the hypothesis that SLE may be based on highly specific abnormalities of immune responses to particular autoantigens, but not on a generalized breakdown of a tolerance mechanism.
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D004198:Disease Susceptibility; D005260:Female; D005808:Genes, Recessive; D007108:Immune Tolerance; D007113:Immunity, Innate; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D008817:Mice, Mutant Strains; D013045:Species Specificity; D014998:Y Chromosome / Q000502:physiology