Demyelination in the central nervous system mediated by an anti-oligodendrocyte antibody

Abstract

The factors responsible for the major demyelinating disease of the central nervous system (CNS), multiple sclerosis, are poorly defined. Although T-cell-mediated immune responses play a pivotal role in establishing the inflammatory response, humoral factors also may be critical in disease progress. We have isolated a mouse monoclonal antibody (mAb 2B10) that recognizes a cell-surface molecule expressed exclusively by rat oligodendrocytes, the cells responsible for the formation and maintenance of CNS myelin. In cultures of neonatal rat spinal cord, mAb 2B10 specifically mediated oligodendrocyte cell death in the absence of complement. In the current study, mAb 2B10-producing hybridoma cells were implanted into adult rat brain ventricles, and the effect of mAb 2B10 on CNS cytoarchitecture was examined. In the optic nerves of mAb 2B10-treated animals, there was significant focal myelin degeneration near the optic chiasm. Axons in the myelin degenerate regions were largely healthy. There was no significant infiltration of hematopoietic-derived cells into the affected regions, but microglia were activated focally and phagocytosed the collapsed myelin. This study demonstrates that an antibody directed against myelin-forming cells induces CNS demyelination and supports the hypothesis that autoantibodies may play a role in CNS demyelinating diseases.

In Vitro Expression of N‐Acetyl Aspartate by Oligodendrocytes

“…The earliest indication of nonneuronal contributions to the changes seen in NAA levels came from the longitudinal studies on MS, which involves demyelination in white matter tracts of the brain. MS is principally a disease involving the destruction of oligodendrocytes, thus leading to demyelination (McMorris and McKinnon, 1996; Raine, 1997; Lucchinetti et al, 1998; Zhou et al, 1998). Using in vivo 1 H MRS to follow changes in NAA during the different phases of MS, Davie et al (1994) demonstrated NAA relative to creatine was reduced in acute lesions, with a subsequent rise in the NAA/creatine ratio.…”

Polyreactive myelin oligodendrocyte glycoprotein antibodies: Implications for systemic autoimmunity in progressive experimental autoimmune encephalomyelitis

“…To determine whether MOG antibody induces demyelination in vivo (Barres et al, 1992;Rosenbluth et al, 1997;Rosenbluth et al, 1999;Schnell and Schwab, 1990;Zhou et al, 1998), we injected 1 × 10 6 MOG antibody producing hybridoma cells, A4ac or A4cd, or 1 × 10 6 isotype control antibody producing hybridoma cells, XMMEN-OE5 (kindly provided by Dr. Moses Rodriguez), in 20 μl of BD Cell Mab Medium into the right cerebral hemisphere or cerebellum of 22 naïve mice (Tsunoda et al, 1996). Mice were killed one week after inoculation.…”

MRI in experimental inflammatory and mitochondrial optic neuropathies

“…There are several animal models of optic neuritis and MS (1,2). They include (a) EAE induced by sensitization of animals to central nervous system (CNS) myelin antigens [myelin basic protein, proteolipid protein, or myelin-associated glycoprotein (2)(3)(4)], (b) viral-induced demyelination (5)(6)(7), and (c) antibody-induced demyelination (8,9). The characteristic relapsing neurological signs of paralysis and visual loss in EAE are similar to those in patients with optic neuritis and MS (10).…”