The role of anti-myelin (auto)-antibodies in the phagocytosis of myelin by macrophages.

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-myelin antibodies are involved in myelin damage. In this study, we have investigated the effect of disease-promoting anti-myelin mAb on the phagocytosis of myelin by macrophages. Monoclonal antibodies directed to myelin basic protein (MBP)--clones 1, 12, 17, 22, 26, proteolipid protein (PLP), galactocerebroside (GalC) and myelin oligodendrocyte glycoprotein (MOG)--clones Y1, Y4, Y6, Y7, Y9, Y10, Y11 and Z12 were incubated with purified murine myelin labeled with DiI. The degree of phagocytosis of antibody-treated myelin by murine macrophages in vitro was determined using a quantitative flow cytometric assay. In comparison to untreated myelin pretreatment with myelin-specific mAb modified the degree of phagocytosis. The degree of opsonization of myelin was dependent on the isotype of antibody and the epitope recognized in addition to the ability of the mAb to fix complement. The greatest degree of opsonization of myelin was observed with the monoclonal antibody MOG Z12 that has previously been shown to enhance EAE and augment demyelination. These findings suggest a major role for anti-myelin antibodies, in particular antibodies directed to MOG, for the phagocytosis of myelin by macrophages in vitro. This may have relevance to the pathogenesis of myelin damage in vivo and provide a helpful tool for the classification of heterogeneous diseases such as MS.