Patients with active relapsing-remitting multiple sclerosis synthesize antibodies recognizing oligodendrocyte progenitor cell surface protein: implications for remyelination.

In multiple sclerosis (MS), remyelination of demyelinated lesions diminishes with disease progression for unknown reasons. Oligodendrocyte progenitor cells contribute to remyelination; however, antibodies specific for oligodendrocyte progenitor antigens could block remyelination by eliminating or impeding these cells. In myelinating cultures, cell lysis with antibody recognizing a progenitor cell-specific surface glycoprotein (AN2) suppressed the synthesis of myelin proteins. Cerebrospinal fluid from patients with relapsing-remitting active MS contains antibodies against AN2, whereas cerebrospinal fluid from patients with nonactive disease does not. This is the first report describing antibodies in MS against a progenitor cell-specific antigen that may contribute to the development and progression of chronically demyelinated lesions.

Monoclonal antibody detects oligodendroglial cell surface protein exhibiting temporal regulation during development.

As tools to study stage-specific surface molecules expressed during the development of oligodendrocytes, we have generated monoclonal antibodies against peanut agglutinin (PNA)-binding glycoproteins isolated by affinity chromatography from the oligodendroglial precursor cell line Oli-neu. In this paper we report the characterization of the monoclonal antibody 7D10. The 7D10 antibody recognizes a 145-kD cell surface glycoprotein expressed by postmitotic multibranched cells of the oligodendroglial lineage. The antigen stains subpopulations of myelin-associated glycoprotein (MAG) and O4-positive cells and is subsequently down-regulated during further differentiation in vitro. The 7D10 antigen is also expressed by a subpopulation of astroglial cells but not by neurons. A truncated form of the protein is released by antigen-expressing cells into the culture supernatant.

Lines of murine oligodendroglial precursor cells immortalized by an activated neu tyrosine kinase show distinct degrees of interaction with axons in vitro and in vivo.

Replication-defective retroviruses expressing the t-neu oncogene, or a hybrid protein with the neu tyrosine kinase linked to the external region of the human epidermal growth factor receptor (egfr-neu), were used to establish lines of murine oligodendroglial precursor cells. Differentiation of the t-neu lines into myelin-associated glycoprotein (MAG)-positive oligodendrocytes was induced by dibutyryl cAMP, and the egfr-neu line showed limited differentiation in vitro upon withdrawal of epidermal growth factor. Cerebellar granule cell neurons expressed mitogens for the cell lines. Upon transplantation into demyelinated lesions, t-neu line cells engaged with the demyelinated axons whereas the egfr-neu line cells differentiated further and ensheathed the axons. These cell lines thus interact with neurons in vitro and in vivo and can be used as tools to define the molecules involved in different stages of neuron-glia interaction.