Novel animal models of acetylcholine receptor antibody–related myasthenia gravis

Experimental autoimmune myasthenia gravis (EAMG) in mice has been used to unravel the pathogenic mechanisms and to be used as a preclinical model of myasthenia gravis (MG). Induction of predominantly ocular EAMG in HLA‐DQ8 transgenic mice immunized with acetylcholine receptor (AChR) subunits demonstrated the importance of nonconformationally expressed AChR subunits in extraocular muscle involvement. Wild‐type (WT) and CD4 + T cell knockout (KO) C57BL/6 mice developed EAMG upon immunization with AChR in incomplete Freund's adjuvant plus lipopolysaccharide. AChR‐specific IgG2 + B cell frequencies, estimated by Alexa‐conjugated AChR, and AChR‐reactive IgG2b levels significantly correlated with the clinical grades of EAMG in WT mice. CD4 + T cell–deficient EAMG mice exhibited AChR antibodies mainly of the IgG2b isotype, emphasizing T helper–independent B cell activation pathways in EAMG induction. These novel EAMG models have suggested that diverse immunopathological mechanisms might contribute to EAMG or MG pathogenesis.