Demyelination induced in aggregating brain cell cultures by a monoclonal antibody against myelin/oligodendrocyte glycoprotein.
A monoclonal antibody (8-18C5) directed against myelin/oligodendrocyte glycoprotein (MOG) induced demyelination in aggregating brain cell cultures. With increasing doses of anti-MOG antibody in the presence of complement, myelin basic protein (MBP) concentration decreased in a dose-related manner. A similar, albeit less pronounced, effect was observed on specific activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase. In the absence of complement, anti-MOG antibody did not induce detectable demyelination. In contrast to the effect of anti-MOG antibody and as expected, anti-MBP antibody did not demyelinate aggregating brain cell cultures in the presence of complement. These results provide additional support to the suggestion that MOG, a quantitatively minor myelin component located on the external side of the myelin membrane, is a good target antigen for antibody-induced demyelination. Indeed, they show that a purified anti-MOG antibody directed against a single epitope on the glycoprotein can produce demyelination, not only in vivo as previously shown, but also in cultures. Such an observation has not been made with polyclonal antisera raised against purified myelin proteins like MBP and proteolipid protein, the major protein components of the myelin membrane, or myelin-associated glycoprotein. These observations may have important implications regarding the possible role of anti-MOG antibodies in demyelinating diseases.
Laboratoire de Neurochimie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
N
N
Kerlero de Rosbo
P
P
Honegger
H
H
Lassmann
J M
JM
Matthieu
D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000941:Antigens / Q000276:immunology; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000276:immunology*; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000276:immunology; D003711:Demyelinating Diseases / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D007074:Immunoglobulin G / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology*; D004676:Myelin Basic Protein / Q000378:metabolism; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000276:immunology* / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010727:Phosphoric Diester Hydrolases; D051381:Rats
D000911:Antibodies, Monoclonal; D000941:Antigens; D000939:Epitopes; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; C571328:Mog protein, rat; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D003165:Complement System Proteins; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D010727:Phosphoric Diester Hydrolases; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571339:Cnp protein, rat