Induction of activation-induced cytidine deaminase gene expression by IL-4 and CD40 ligation is dependent on STAT6 and NFκB
Induction of activation-induced cytidine deaminase gene expression by IL-4 and CD40 ligation is dependent on STAT6 and NFκB
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DOI：
10.1093/intimm/dxh042
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发表时间：
2004-03-01
影响因子：
4.4
通讯作者：
Geha, RS
中科院分区：
文献类型：
--
作者：
Dedeoglu, F;Horwitz, B;Geha, RS
活化诱导胞苷脱氨酶（AID）是一种可诱导基因，在B细胞的类别转换重组、体细胞高频突变和基因转换中发挥重要作用。我们研究了白细胞介素 - 4（IL - 4）和CD40连接对人和小鼠B细胞中AID基因表达的调控。IL - 4自身以及在较小程度上CD40连接可诱导原代B细胞中AID mRNA的表达。这两种刺激在诱导AID mRNA和蛋白质表达方面具有强烈的协同作用。IL - 4诱导STAT6与AID基因5'上游区域的一个位点结合，而CD40连接诱导NF - κB与该区域的两个位点结合。来自STAT6（ - / - ）小鼠的B细胞不能对IL - 4作出上调AID的反应，而来自p50（ - / - ）小鼠的B细胞在对CD40连接和IL - 4作出上调AID的反应能力上受损。这些结果表明，通过激活NF - κB的CD40传递的信号与通过激活STAT6的IL - 4受体传递的信号协同作用，以诱导最佳的AID基因表达。
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.