LEWIS RATS GIVEN ANTIBODIES AGAINST DENATURED ACETYLCHOLINE-RECEPTOR BECOME RESISTANT TO INDUCTION OF EXPERIMENTAL AUTOIMMUNE MYASTHENIA-GRAVIS

Experimental autoimmune myasthenia gravis (EAMG) in rats can be produc ed as the result of immunization with purified acetylcholine receptor (AChR). However antibodies produced against an irreversibly denatured AChR were not capable of producing detectable AChR-dependent neuromusc ular impairment such as that seen following immunization with AChR of intact conformation. This immunopathological difference was observed d espite the fact that both immunizations: resulted in the production of clonotypically heterogeneous antibodies with similar titers, isotype distribution, and relative binding avidities for conformationally inta ct AChR. Although they had no apparent disease-causing potential of th eir own, antibodies produced against denatured AChR could, however, bi nd AChR at the neuromuscular junction and mediate in vivo AChR-depende nt neuromuscular impairment if a second anti-antibody was provided, Fi nally, immunization against denatured AChR, or administration to naive rats: of antibodies obtained by immunization against denatured AChR, resulted in the recipient rats becoming resistant to the usual patholo gical effects of antibodies produced against intact AChR (either induc ed by active immunization or following passive antibody transfer). The se observations suggest that disease severity in this system may be in fluenced by relationships between disease causing and disease-abrogati ng antibodies. (C) 1996 Academic Press, Inc.