AID-mediated diversification within the IgL locus of chicken DT40 cells is restricted to the transcribed IgL gene
AID-mediated diversification within the IgL locus of chicken DT40 cells is restricted to the transcribed IgL gene
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DOI：
10.1016/j.molimm.2007.10.017
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发表时间：
2008-04-01
影响因子：
3.6
通讯作者：
Fugmann, Sebastian D.
中科院分区：
文献类型：
--
作者：
Gopal, Anjali R.;Fugmann, Sebastian D.
体细胞超突变(SHM)和基因转换(GCV)是密切相关的过程，它们增加了初级免疫球蛋白谱系的多样性。在这两个过程中，激活诱导的胞苷脱氨酶(AID)以转录依赖的方式将免疫球蛋白(Ig)基因DNA中的胞嘧啶残基转化为尿嘧啶，随后容易出错的修复过程导致编码受体的抗原识别位点发生变化。这种活性被未知的机制特异性地招募到免疫球蛋白基因座上。我们对鸡B细胞系DT40及其衍生物的分析表明，即使是免疫球蛋白轻链(IGL)基因的最接近的邻居也受到保护，尽管它是转录的，因此是AID的潜在靶点。我们的发现支持一个模型，在该模型中，顺式作用的DNA边界元件将AID活性限制在IGL基因座，并保护IGL基因附近的基因组免受有害突变。爱思唯尔有限公司出版。
Somatic hypermutation (SHM) and gene conversion (GCV) are closely related processes that increase the diversity the primary immunoglobulin repertoire. In both processes the activation-induced cytidine deaminase (AID) converts cytosine residues to uracils within the DNA of the immunoglobulin (Ig) genes in a transcription-dependent manner, and subsequent error-prone repair processes lead to changes in the antigen recognition site of the encoded receptors. This activity is specifically recruited to the Ig loci by unknown mechanisms. Our analyses of the chicken B-cell line DT40, and derivatives thereof, now revealed that even the closest neighbors of the Ig light chain (IgL) gene are protected from AID activity, albeit being transcribed and thus acting as potential targets of AID. Our findings are in support of a model in which cis-acting DNA boundary elements restrict AID activity to the IgL locus and guard the genome in the vicinity of the IgL gene from deleterious mutations. Published by Elsevier Ltd.