CD40 ligation and IL-4 use different mechanisms of transcriptional activation of the human lymphotoxin alpha promoter in B cells

European Journal of Immunology
M WormR S Geha

Abstract

We have previously shown that both CD40 ligation and IL-4 induce lymphotoxin alpha (LT alpha) expression in B cells. We generated a series of truncations of the LT alpha upstream region (-915 to +7 bp) and examined their ability to drive expression of a luciferase (LUC) reporter gene in B cells. The CD40-responsive promoter region of LT alpha was mapped to the region spanning -120 to -52 bp. This region contains an NF-kappa B site (-99 to -89 bp) which was shown to form a complex with nucleoproteins from CD40-stimulated B cells that contained the p50/p65 subunits of NF-kappa B. Mutation of the NF-kappa B site within the -356 to +7 bp region of the LT alpha gene completely abolished its capacity to drive transcription of the LUC gene in response to stimulation with CD40, but not to IL-4. The IL-4-responsive promoter region of LT alpha was mapped to the region spanning -265 to -185 bp. This region contains a site for binding to signal transducers and activators of transcription (STAT) proteins (-197 to -189 bp). This site was shown to form a complex with nucleoproteins from IL-4-stimulated B cells that contained STAT6. Mutation of the STAT site within the -356 to +7 bp region of the LT alpha gene completely abolished its capacity...Continue Reading

References

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Citations

Dec 14, 2001·Biochemical and Biophysical Research Communications·W XuX Liu
Mar 18, 2005·Annual Review of Immunology·Carl F Ware
Jul 14, 2012·Journal of the International AIDS Society·Iain J MacLeodRoger L Shapiro
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Sep 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhi ChenRiitta Lahesmaa
Mar 12, 2010·Nature·Massimo AmmiranteMichael Karin
Jan 23, 2008·Laboratory Investigation; a Journal of Technical Methods and Pathology·George P ChristophiPaul T Massa
Jul 29, 2005·Immunological Reviews·Rodney D Newberry, Robin G Lorenz
Apr 3, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Brian H YokleyPhillip E Posch
Nov 17, 2004·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·N M HellerR P Schleimer

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