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Int Immunol. 2004 Mar;16(3):395-404.

Induction of activation-induced cytidine deaminase gene expression by IL-4 and CD40 ligation is dependent on STAT6 and NFkappaB.

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1
Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School, Harvard Medical School, Boston, MA 02115, USA.

Abstract

Activation-induced cytidine deaminase (AID) is an inducible gene that plays an important role in class switch recombination, somatic hypermutation and gene conversion in B cells. We examined the regulation of AID gene expression in human and mouse B cells by IL-4 and CD40 ligation. IL-4 by itself and, to a much lesser extent, CD40 ligation induced AID mRNA expression in primary B cells. The two stimuli strongly synergized in inducing AID mRNA and protein expression. IL-4 induced STAT6 binding to a site in the 5' upstream region of the AID gene, while CD40 ligation induced NFkappaB binding to two sites in that region. B cells from STAT6-/- mice failed to up-regulate AID in response to IL-4, while B cells from p50-/- mice were impaired in their ability to up-regulate AID in response to CD40 ligation and IL-4. These results suggest that signals delivered via CD40 that activate NFkappaB synergize with signals delivered via the IL-4 receptor that activate STAT6 to induce optimal AID gene expression.

PMID:
14978013
[Indexed for MEDLINE]
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