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 progenitor s in the presence of a monoclonal antibody (R-mAb) reacting with a cel l surface component reversibly blocks their further differentiation at a specific, late progenitor stage of the lineage. This block is chara cterized by a nearly complete elimination of the onset of terminal dif ferentiation at the level of RNA expression. In the present study, mat ure oligodendrocytes already expressing markers of terminal differenti ation were exposed to R-mAb. This resulted in a retraction of cell pro cesses and the formation of round, swollen cells, and a dose-dependent , antibody-specific partial reduction (30-50%) in the steady state lev els of markers of terminal differentiation. Upon removing the perturbi ng antibody, all markers returned to control levels within 2 days. Thi s inhibition was due to modulations of the levels of the specific mRNA s and proteins, not to cell loss. Total protein and levels of a marker of astrocytic differentiation were not affected by the treatment. Mon oclonal antibody O1 did not cause the effects observed with R-mAb. We conclude that the response of terminally differentiating oligodendrocy tes to the effects of R-mAb is different from that of oligodendrocyte late progenitors. Whereas the latter appears to operate through pertur bation of the onset of gene expression (mRNA transcription and/or stab ility), the partial down-regulation of previously activated myelinogen ic gene expression appears to be due to the loss of a normal, myelin-l ike, membrane environment needed for the stability of myelin mRNA and protein components. (C) 1994 Wiley-Liss, Inc.