Negative regulation of the interleukin (IL)-2 receptor alpha chain (CD25) promoter region in human B lymphocytes

Abstract

Studies of the CD25 gene promoter region in T cells have revealed the presence of a 31-bp region, including an 11-bp negative regulatory element (NRE), which profoundly suppresses CD25 expression. This report illustrates that the same region acts as a negative regulator of CD25 expression in human B lymphocytes. Human B cells contain DNA-binding protein activities which bind specifically to an oligonucleotide equivalent to the 11-bp core region of the NRE, and stimulation of tonsillar B cells or Daudi Burkitt's lymphoma B cells with interleukin 4 (IL-4) results in loss of binding activity for oligonucleotides containing the NRE; in contrast, IL-4 enhanced binding activity for the NRE in the Jurkat T cell line. Transient transfection analyses using deletion mutants lacking both the 11-bp core NRE and both the NRE and an adjacent putative retinoic acid response element (RARE) motif illustrated that the NRE element is a functional suppressor of CD25 transcription in B cells. Thus, deletion of the NRE element increased the basal level of CD25 promoter activity and also conferred IL-4 inducibility on reporter gene expression in transiently transfected tonsillar B lymphocytes.