IL-4-stimulated NF-kappaB activity is required for Stat6 DNA binding.

IL-4 is a critical cytokine in the regulation of immune responses. In B lymphocytes, IL-4 signaling promotes the Stat6-dependent cell surface expression of several proteins including MHC Class II and CD86. However, the requirement for other transcription factors in IL-4-induced B cell gene expression has not been studied extensively. Here, we show that IL-4 induces NF-kappaB p100 processing to NF-kappaB p52 in B cells but not in T cells or macrophages. IL-4 induced NF-kappaB p52 production requires PI-3K activity and correlates with IkappaB kinase phosphorylation and TNF receptor-associated factor 3 degradation. Blocking NF-kappaB activity eliminates IL-4-stimulated gene expression in B cells by reducing IL-4-induced DNA binding but not phosphorylation or nuclear localization of Stat6. These results describe a novel role for NF-kappaB in IL-4-induced signaling and gene expression.