THE HUMAN SEVERE COMBINED IMMUNODEFICIENCY MYASTHENIC MOUSE MODEL - ANEW APPROACH FOR THE STUDY OF MYASTHENIA-GRAVIS

We have established a new chimeric human-mouse model of myasthenia gra vis in severe combined immunodeficiency mice, using human peripheral b lood lymphocytes that survive in the mouse and produce specific antibo dies that mediate pathological changes typical of human myasthenia gra vis. Mice given peripheral blood lymphocytes from both anti-acetylchol ine receptor (AChR) antibody-positive and -negative patients with myas thenia gravis showed circulating anti-acetylcholine receptor antibodie s, deposition of human IgG at muscle end-plates, and simplification of the postsynaptic membrane, findings characteristic of human myastheni a gravis. Mice given human peripheral blood lymphocytes from healthy d onors and simultaneously immunized with Torpedo acetylcholine receptor showed the same changes. This chimeric model, utilizing human cells t o reproduce the immunopathological findings of human myasthenia gravis in a nonhuman environment, offers new opportunities to study immune r egulation in autoimmunity.