IL‐4‐stimulated NF‐κB 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‐κB p100 processing to NF‐κB p52 in B cells but not in T cells or macrophages. IL‐4 induced NF‐κB p52 production requires PI‐3K activity and correlates with IκB kinase phosphorylation and TNF receptor‐associated factor 3 degradation. Blocking NF‐κB 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‐κB in IL‐4‐induced signaling and gene expression.