International Immunology, Vol. 16, No. 3, pp. 395-404,
March 2004
© 2004 Japanese Society for Immunology
Induction of activation-induced cytidine deaminase gene expression by IL-4 and CD40 ligation is dependent on STAT6 and NF
B
1 Division of Immunology, Children’s Hospital and Department of Pediatrics, Harvard Medical School, 2 Brigham and Women Hospital and 3 Howard Hughes Institute, Harvard Medical School, Boston, MA 02115, USA
Correspondence to: R. S. Geha; E-mail: raif.geha{at}tch.harvard.edu
Transmitting editor: F. S. Rosen
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 NF
B 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 NFB synergize with signals delivered via the IL-4 receptor that activate STAT6 to induce optimal AID gene expression.
Keywords: B lymphocyte, class switch recombination, gene expression
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