The role of anti-myelin (auto)-antibodies in the phagocytosis of myelin bymacrophages

Plasma cells secreting antibodies directed to myelin components are present in CNS of MS patients and although the pathogenic role of such antibodies has yet to be established it is apparent from animal studies that anti-myel in antibodies are involved in myelin damage. In this study, we have investi gated the effect of disease-promoting anti-myelin mAb on the phagocytosis o f myelin by macrophages. Monoclonal antibodies directed to myelin basic pro tein (MBP) - clones 1, 12, 17, 22, 26, proteolipid protein (PLP), galactoce rebroside (GalC) and myelin oligodendrocyte glycoprotein (MOG) - clones Y1, Y4, Y6, Y7, Y9, Y10, Y11 and Z12 were incubated with purified murine myeli n labeled with DiI. The degree of phagocytosis of antibody-treated myelin b y murine macrophages in vitro was determined using a quantitative flow cyto metric assay. In comparison to untreated myelin pretreatment with myelin-sp ecific mAb modified the degree of phagocytosis. The degree of opsonization of myelin was dependent on the isotype of antibody and the epitope recogniz ed in addition to the ability of the mAb to fix complement. The greatest de gree of opsonization of myelin was observed with the monoclonal antibody MO G Z12 that has previously been shown to enhance EAE and augment demyelinati on. These findings suggest a major role for anti-myelin antibodies, in part icular antibodies directed to MOG, for the phagocytosis of myelin by macrop hages in vitro. This may have relevance to the pathogenesis of myelin damag e in vivo and provide a helpful tool for the classification of heterogeneou s diseases such as MS. (C) 1999 Elsevier Science B.V. All rights reserved.