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.