A MODEL OF PEPTIDE-INDUCED LUPUS AUTOIMMUNE B-CELL EPITOPE SPREADING IS STRAIN-SPECIFIC AND IS NOT H-2 RESTRICTED IN MICE

Anti-Sm is a common and specific autoantibody found in systemic lupus erythematosus. The peptide PPPGMRPP from Sm B/B' is an early target of the autoimmune response in some anti-Sm-positive human patients, Afte r immunization with this peptide on a MAP backbone, rabbits develop an ti-Sm autoantibodies with B cell epitope spreading of the autoimmune r esponse as well as other features of lupus autoimmunity, Various strai ns of inbred mice have been immunized with peptide PPPGMRPP or PSQQVMT P (nonantigenic region of Sm B/B') in Freund's adjuvant or with no pep tide, All peptide-immunized mouse strains eventually develop high tite rs of specific anti-peptide of immunization Abs, Mice immunized with F reund's adjuvant alone have no measurable Ab binding to the PPPGMRPP p eptide, With time, nearly half the mouse strains tested develop Abs th at react with additional regions of Sm B/B' and Sm D, All the regions bound by mouse serum are major epitopes of the human systemic lupus er ythematosus anti-Sm response. These same strains also develop signific ant anti-gm and anti-nuclear ribonucleoprotein titers, In addition, so me of these strains demonstrate positive anti-nuclear Abs and anti-dsD NA Abs, Experiments with congenic H-2 mice demonstrate that the H-2 re gion does not play a role in spreading the immune response from the pe ptide of immunization to other epitopes of the spliceosome. These resu lts present a new murine model of B cell epitope spreading and lupus a utoimmunity induced by peptide immunization that is strain specific an d not apparently dependent upon the loci at H-2.