Activation-induced cytidine deaminase (AID) promotes B cell lymphomagenesis in Emu-cmyc transgenic mice
Activation-induced cytidine deaminase (AID) promotes B cell lymphomagenesis in Emu-cmyc transgenic mice
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DOI：
10.1073/pnas.0610732104
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发表时间：
2007-01-30
影响因子：
11.1
通讯作者：
Honjo, Tasuku
中科院分区：
文献类型：
--
作者：
Kotani, Ai;Kakazu, Naoki;Honjo, Tasuku
激活诱导的胞苷脱氨酶 (AID) 对于 Ig 基因的类别转换重组和体细胞超突变至关重要，在多种类型的人类 B 细胞淋巴瘤/白血病中表达。 AID 是一种有效的突变因子，因为它不仅涉及 Ig 的 DNA 断裂，还涉及其他基因（包括原癌基因）的 DNA 断裂。最近的研究表明，涉及 cmyc 和 Ig 位点的染色体易位需要 AID。然而，目前尚不清楚AID是否在肿瘤发生中发挥其他作用。我们研究了 AID 缺陷对 Emu-cmyc 转基因小鼠表面 Ig 阳性 B 细胞淋巴瘤产生的影响。几乎所有在 AID 缺陷的转基因小鼠中发生的淋巴瘤都是前 B 细胞淋巴瘤，而对照转基因小鼠主要具有 B 细胞淋巴瘤，这表明 AID 是 B 细胞发育所必需的，而不是 cmyc 过表达肿瘤祖细胞的前 B 细胞淋巴瘤的发生所必需的。因此，AID可能在B细胞淋巴瘤发生中发挥多种作用。
Activation-induced cytidine deaminase (AID), which is essential to both class switch recombination and somatic hypermutation of the Ig gene, is expressed in many types of human B cell lymphoma/ leukemia. AID is a potent mutator because it is involved in DNA breakage not only of Ig but also of other genes, including proto-oncogenes. Recent studies suggest that AID is required for chromosomal translocation involving cmyc and Ig loci. However, it is unclear whether AID plays other roles in tumorigenesis. We examined the effect of AID deficiency on the generation of surface Ig-positive B cell lymphomas in Emu-cmyc transgenic mice. Almost all lymphomas that developed in AID-deficient transgenic mice were pre-B cell lymphomas, whereas control transgenic mice had predominantly B cell lymphomas, indicating that AID is required for development of B but not pre-B cell lymphomas from cmyc overexpressing tumor progenitors. Thus, AID may play multiple roles in B cell lymphomagenesis.