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

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.