Interferon-alpha promotes survival of human primary B-lymphocytes via phosphatidylinositol 3-kinase

Signaling pathways for the antiviral and antiproliferative biological effec ts of type I interferons (IFN) are well established. In this report we demo nstrate a novel signaling pathway for IFN-alpha, as it induced rapid phosph orylation of both PKB/Akt and its substrate fork-head. The PI3-kinase inhib itor LY294002 abolished these phosphorylations, PI3-kinase has been implica ted in cell survival mediating its effect through the second messenger PIP3 and the subsequent activation of PKB/Akt. We could show that IFN-alpha inh ibited spontaneous apoptosis of primary B-lymphocytes, in the absence of a mitogenic stimulus. This effect was inhibited by LY294002. Thus, our data s uggests that IFN-alpha promotes survival of peripheral B-lymphocytes via th e PI3-kinase-PKB/Akt pathway. In addition, IFN-alpha stimulation of anti-Ig M activated cells resulted in downregulated expression of the cell cycle in hibitor p27/Kip1. (C) 2001 Academic Press.