Multi-organ reactivity of a monoclonal natural autoantibody that promotes remyelination in a mouse model of multiple sclerosis.

A contemporary view of autoimmunity suggests that self-reactivity is a normal phenomenon, in contrast to the classical association between autoimmunity and immunopathology. We have previously demonstrated that monoclonal antibody SCH94.03, a natural autoantibody with polyreactivity towards several purified protein and hapten antigens, promotes central nervous system remyelination when passively transferred to SJL/J mice chronically infected with Theiler's murine encephalomyelitis virus, an established experimental model of multiple sclerosis. In this study we characterized the autoreactivity of SCH94.03 with endogenous mouse tissue using immunoperoxide and multiple-color immunofluorescence staining techniques on frozen tissue sections. Within the nervous system, SCH94.03 labeled fibrous astrocytes, ependymal cells, ganglion satellite cells, and a sub-population of microglia, oligodendrocytes, and peripheral nervous system neurons. Outside the nervous system, SCH94.03 labeled gastrointestinal tract smooth muscle and luminal epithelium, erythrocytes, and interdigitating dendritic cells in peripheral lymphoid organs. These data indicate that SCH94.03 is a multi-organ reactive autoantibody and support the hypothesis that autoantibodies can have a beneficial rather than a pathogenic function in central nervous system demyelinating diseases.