Negative regulation of activation-induced cytidine deaminase in B cells
Negative regulation of activation-induced cytidine deaminase in B cells
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DOI：
10.1073/pnas.0510970103
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发表时间：
2006-02-21
影响因子：
11.1
通讯作者：
Honjo, T
中科院分区：
文献类型：
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作者：
Muto, T;Okazaki, IM;Honjo, T
Ig基因的类开关重组(CSR)和体细胞超突变(SHIM)都需要激活诱导型胞苷脱氨酶(AID)的活性。AID的表达仅限于淋巴器官生发中心的B细胞，在那里激活的B细胞经历CSR和SHM。我们先前的研究表明，AID的结构性和系统性表达会导致T细胞和肺上皮细胞发生肿瘤，但不会导致B细胞发生肿瘤。这一发现使我们怀疑转基因AID可能至少在B细胞中部分失活。为了解决这个问题，我们产生了条件性AID转基因小鼠，这些小鼠仅在B细胞中结构性地表达AID。对AID转基因小鼠与AID缺陷小鼠杂交的研究表明，在B细胞中，通过结构性表达积累的丰富的AID蛋白被灭活，这可能为AID转基因B细胞中没有解除CSR和SHM调控提供了解释。
Both class switch recombination (CSR) and somatic hypermutation (SHIM) of the Ig genes require the activity of activation-induced cytidine deaminase (AID). Expression of AID is restricted to B cells in the germinal centers of the lymphoid organs, where activated B cells undergo CSR and SHM. We previously showed that constitutive and systemic expression of AID leads to tumorigenesis in T cells and lung epithelium, but not in B cells. This finding led us to suspect that transgenic AID may be inactivated at least in part in B cells. To address this issue, we generated conditional AID-transgenic mice that constitutively express AID only in B cells. Studies on the cross between the AID-transgenic and AID-deficient mice showed that abundant AID protein accumulated by constitutive expression is inactivated in B cells, possibly providing an explanation for the absence of deregulation of CSR and SHM in AID-transgenic B cells.