Regulation of gene expression in mature oligodendrocytes by the specialized myelin‐like membrane environment: Antibody perturbation in culture with the monoclonal antibody R‐mAb

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Abstract
We have previously shown that the growth of oligodendrocyte progenitors in the presence of a monoclonal antibody (R‐mAb) reacting with a cell surface component reversibly blocks their further differentiation at a specific, late progenitor stage of the lineage. This block is characterized by a nearly complete elimination of the onset of terminal differentiation at the level of RNA expression. In the present study, mature oligodendrocytes already expressing markers of terminal differentiation were exposed to R‐mAb. This resulted in a retraction of cell processes and the formation of round, swollen cells, and a dose‐dependent, antibody‐specific partial reduction (30‐50%) in the steady state levels of markers of terminal differentiation. Upon removing the perturbing antibody, all markers returned to control levels within 2 days. This inhibition was due to modulations of the levels of the specific mRNAs and proteins, not to cell loss. Total protein and levels of a marker of astrocytic differentiation were not affected by the treatment. Monoclonal antibody O1 did not cause the effects observed with R‐mAb. We conclude that the response of terminally differentiating oligodendrocytes to the effects of R‐mAb is different from that of oligodendrocyte late progenitors. Whereas the latter appears to operate through perturbation of the onset of gene expression (mRNA transcription and/or stability), the partial down‐regulation of previously activated myelinogenic gene expression appears to be due to the loss of a normal, myelin‐like, membrane environment needed for the stability of myelin mRNA and protein components.

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