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A popular mouse model, experimental autoimmune encephalomyelitis (EAE), could serve to develop such a therapy, provided we can better understand the nature and importance of the autoantibodies involved. Here we report the discovery of autoantibody-secreting extrafollicular plasmablasts in EAE induced with specific myelin oligodendrocyte glycoprotein (MOG) antigens. Single-cell RNA sequencing reveals that these cells produce non-affinity-matured IgG antibodies. These include pathogenic antibodies competing for shared binding space on MOG\u2019s extracellular domain. Interestingly, the synthetic anti-MOG antibody 8-18C5 can prevent the binding of pathogenic antibodies from either EAE mice or people with MOG antibody disease (MOGAD). Moreover, an 8-18C5 variant carrying the NNAS mutation, which inactivates its effector functions, can reduce EAE severity and promote functional recovery. 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