Down-regulation of CD5 mRNA in B-chronic lymphocytic leukemia cells by differentiation-inducing agents

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Abstract
Most B chronic lymphocytic leukemia (CLL) cells express on their surface the CD5 antigen which is an activation marker on normal B cells. To investigate the control of CD5 expression in B‐CLL cells, we examined several inducing agents for their effects on CD5 mRNA expression. Northern blot analysis demonstrated that the expression of CD5 mRNA could be up‐ or down‐regulated depending on the inducers used. Treatment with direct activators of protein kinase C (PKC), the phorbol ester phorbol 12‐myristate 13‐acetate (PMA) or the natural agent bryostatin 1 (Bryo), caused increased CD5 mRNA expression after 8—16 h of incubation. In contrast, exposure to the dual signals of a PKC activator (PMA or Bryo) plus the calcium ionophore A23187 led to down‐regulation of CD5 mRNA expression. The molecular alterations at the RNA level were accompanied by morphological changes: PMA and/or Bryo induced cellular features of activation while PMA plus A23187 or Bryo plus A23187 mediated morphological changes indicativeof differentiation to plasmacytoid cells. The data suggest that as a consequence of maturation differentiated B‐CLL cells down‐regulate CD5 expression by analogy with the normal ontogenic process in which plasma cells, the end‐stage cells of normal B cell differentiation, are CD5−.