Interferon and phorbol esters down‐regulate slgM expression by independent pathways

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Abstract
We studied the effects of recombinant, interferon, 12-O-tetradecanoylphorbol13-acetate (TPA), and phorbol 12,13 dibutyrate (PDB) on surface immunoglobulin expression by Daudi cells. Incubation of cells with recombinant alpha2interferon (IFN-α2) caused a 2.5-fold (60%) decrease in slgM expression as measured by relative fluorescence index (RFI) using a flow cytometer. This decrease in slgM expression was independent of inhibitory effects on proliferation and cell cycle progression. TPA or PDB also caused a threefold (67%) decrease in slgM expression, while enhancing proliferation and cell cycle progression. Coincubation of cells with IFN-α2 or TPA decreased slgM expression by more than fourfold (>75%), which was greater than the decrease induced by the optimal concentration of either agent alone. Molecular studies demonstrated that the treatment of cells with IFN-α2 or TPA decreased the steady-state levels of mRNA for the heavy chain of IgM (cμ), suggesting that down-regulation of slgM occurred at a pretranslational level. Activation of the cell membrane sodium/proton antiport did not play an integral role in the IFN-α2 or phorbol-ester-induced pathway of slgM down-regulation. Whereas IFN-α2 induced an increase in the activity of 2′,5′-oligoadenylate (2–5A) synthetase, the addition of TPA to IFN-α2 caused a significant decrease in the activity of this enzyme. Although IFN-α2 and TPA exhibited additive effects on slgM expression, they had opposing effects on cell proliferation, cell cycle progression, and induction of 2–5A synthetase activity, suggesting that these agents down-regulate slgM expression through independent pathways.