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Multiple sclerosis is a progressive neurological disorder that results in the degradation of myelin sheaths that insulate axons in the central nervous system. Two mouse monoclonal natural autoantibodies, O1 and O4, can promote myelin repair in several mouse models of multiple sclerosis. O1 and O4 monoclonal antibodies serve as stage-specific markers of oligodendrocyte development with O4 marking early oligodendrocyte progenitors and O1-labeling late oligodendrocyte progenitors. O4-positive cells differentiate to become O1-positive, which can in turn become mature oligodendrocytes.