Involvement of nuclear factor-kappa B activation in IgE synthesis in human B cells.
Nuclear factor-kappa B (NF-kappa B) is a transcription factor that binds to the consensus DNA sequence in the cis-acting elements of various genes. Although NF-kappa B activates the expression of many genes involved in immune and inflammatory responses, little is known about the role of NF-kappa B activation in the induction of IgE synthesis in human B cells. Therefore we first examined the participation of NF-kappa B in germline C epsilon transcription in a human Burkitt lymphoma B cell line, DND39. Stimulation of DND39 cells with IL-4 or anti-CD40 monoclonal antibody (mAb) activated phosphatidylinositol 3-kinase and subsequently induced nuclear expression of NF-kappa B, which was identified by electrophoretic mobility shift assays. n-Acetyl-L-cysteine (NAC), a potent antioxidant, blocked NF-kappa B activation caused by IL-4 and by anti-CD40 mAb. Although inhibition of IL-4-driven germline C epsilon transcription by NAC was not sufficient, the agent remarkably diminished anti-CD40 mAb-mediated up-regulation of germline C epsilon transcription. Second, we studied the effect of NAC on IgE synthesis in human normal B cells costimulated with IL-4 and anti-CD40 mAb. NAC was effective in inhibiting mature C epsilon transcription and IgE synthesis in the T cell-independent culture system. However, NAC did not significantly affect the spontaneous production of IgE by atopic B cells. These results indicate that NF-kappa B activity is commonly inducible in DND39 cells by IL-4 and anti-CD40 mAb and suggest that NF-kappa B sensitive to NAC may play a role in regulating IgE synthesis in B cells.
Yanagihara
Y
Y
Clinical Research Center for Allergy, National Sagamihara Hospital, Kanagawa, Japan.
Basaki
Y
Y
Ikizawa
K
K
Kajiwara
K
K
Koshio
T
T
Akiyama
K
K
D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*
D016328:NF-kappa B; D007073:Immunoglobulin E