Possible Role of Nuclear Factor-κB Activity in Germline Cϵ Transcription in a Human Burkitt Lymphoma B Cell Line

Nuclear factor-κB (NF-κB) plays a broad role in gene regulation, but it is not evident whether NF-κB acts as a messenger system for germline Cϵ transcription. We report here that the signaling cascade triggered by interleukin-4 (IL-4) or anti-CD40 monoclonal antibody (mAb) participates in NF-κB activation responsible for germline Cϵ transcription in a human Burkitt lymphoma B cell line, DND39. Both IL-4 and anti-CD40 mAb induced activation of phosphatidylinositol 3-kinase (PI3-kinase), translocation of a ζ isoform of protein kinase C, and nuclear expression of NF-κB. All such events were abrogated by treatment with LY294002, a specific inhibitor of PI3-kinase. In addition,N-acetyl-l-cysteine (NAC), a potent antioxidant, decreased NF-κB activation caused by IL-4, anti-CD40 mAb, or their combination. NAC was also effective in diminishing germline Cϵ transcription, and its potency was higher in cultures costimulated with IL-4 and anti-CD40 mAb than in those stimulated with IL-4 alone. These results indicate that IL-4 and ligation of CD40 induce NF-κB expression via at least a mechanism dependent on the PI3-kinase pathway and suggest that NF-κB sensitive to NAC may play a role in regulating germline Cϵ transcription.