MONOCLONAL AUTOANTIBODY SCH94.03, WHICH PROMOTES CENTRAL-NERVOUS-SYSTEM REMYELINATION, RECOGNIZES AN ANTIGEN ON THE SURFACE OF OLIGODENDROCYTES

A monoclonal antibody SCH94.03, made in syngeneic mice by injection of spinal cord homogenate, promotes central nervous system remyelination when injected into SJL/J mice chronically infected with Theiler's vir us. To elucidate the mechanism of antibody-mediated remyelination, SCH 94.03 was investigated by immunocytochemistry, flow cytometry, immunoe lectron microscopy, Western blotting, and immune-thin layer chromatogr aphy. All cell types investigated in vitro showed strong cytoplasmic s taining with a pattern resembling a cytoskeletal protein. In contrast, among the primary cultured cells studied, only oligodendrocytes showe d strong surface reactivity. Other cell types, including astrocytes, m icroglia, Schwann cells, myoblasts, and T and B lymphocytes, were nega tive. Mouse and rat oligodendrocytes which showed strong surface react ivity exhibited a well-differentiated morphology, and similar to 50% e xpressed myelin basic protein. Since oligodendrocyte progenitors were negative for surface staining, the expression of the antigens recogniz ed by this monoclonal antibody appears to be developmentally regulated , i.e., transiently expressed on younger, terminally differentiating o ligodendrocytes. Among the cell lines studied, only two rat oligodendr ocyte lineage cell lines showed surface reactivity with SCH 94.03. Wes tern blotting of secondary isolated oligodendrocytes lysates revealed reactivity with multiple protein bands of 27, 32, 50, 100, and 106 kDa , whereas there was no reactivity to lipid antigens by immune-thin lay er chromatography. These results raise the possibility that SCH94.03 r ecognizes a novel oligodendrocyte-specific surface antigen, and may ac t directly on oligodendrocytes to promote remyelination. (C) 1996 Wile y-Liss, Inc.