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doi: 10.1093/intimm/dxh042 Induction of activation-induced cytidine

Summary: doi: 10.1093/intimm/dxh042
Induction of activation-induced cytidine
deaminase gene expression by IL-4 and
CD40 ligation is dependent on STAT6 and
Fatma Dedeoglu1, Bruce Horwitz2, Jayanta Chaudhuri3, Frederick W. Alt3 and
Raif S. Geha1
1Division of Immunology, Children's Hospital and Department of Pediatrics, Harvard Medical School,
2Brigham and Women Hospital and 3Howard Hughes Institute, Harvard Medical School, Boston, MA
02115, USA
Keywords: B lymphocyte, class switch recombination, gene expression
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 NFkB 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


Source: Alt,, Frederick - Immune Disease Institute, Harvard University


Collections: Biology and Medicine