THE HUMAN IGE GERMLINE PROMOTER IS REGULATED BY INTERLEUKIN-4, INTERLEUKIN-13, INTERFERON-ALPHA AND INTERFERON-GAMMA VIA AN INTERFERON-GAMMA-ACTIVATED SITE AND ITS FLANKING REGIONS

Class switching to IgE is preceded by the appearance of epsilon germli ne transcripts, which are induced by Interleukin-4 (IL-4) and by IL-13 . A 51-bp fragment of the human epsilon germline promoter conferred in reporter gene assays with the erythroleukemic cell line TF-1 upregula tion of transcription by IL-4 or IL-13, and repression by interferon-a lpha (IFN-alpha) and IFN-gamma. A central IFN-gamma activated sequence within the 51-bp fragment was sufficient for transcriptional regulati on by the cytokines in the absence of its normal flanking regions. In contrast, deletion of either upstream or downstream sequences abolishe d repression by IFN-alpha or INF-gamma, but not upregulation by IL-4 o r IL-13. IL-4 stimulated reporter gene transcription required more tha n ten times higher concentrations than cell proliferation or tyrosine phosphorylation of the IL-4 receptor.