Essential roles of the κ light chain intronic enhancer and 3′ enhancer in κ rearrangement and demethylation

Essential roles of the κ light chain intronic enhancer and 3′ enhancer in κ rearrangement and demethylation
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DOI:
10.1038/ni790
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发表时间:
2002-05-01
期刊:
影响因子:
30.5
通讯作者:
Xu, Y
Xu, Y
中科院分区:
医学1区
文献类型:
--
作者:
Inlay, M;Alt, FW;Xu, Y

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kappa内含子(MiE(kappa))和3'(3' E-kappa)增强子对于免疫球蛋白kappa重排都是定量重要的,但不是必需的。为了确定这两个增强子之间的功能冗余,分析了来自突变胚胎干细胞的B细胞的kappa重排,其中MiE(kappa)和3 'E-kappa在两个kappa等位基因上都缺失。我们的研究结果表明,这些双突变B细胞基本上没有kappa重排,但重排和表达λ。因此,这两个kappa增强子在激活V(kappa)J(kappa)重排中具有重要作用。我们的研究结果还表明,这两个kappa增强子在B细胞中kappa的去甲基化中发挥重叠和不同的作用。
The kappa intronic (MiE(kappa)) and 3' (3'E-kappa) enhancers are both quantitatively important to, but not essential for, immunoglobulin kappa rearrangement. To determine the functional redundancy between these two enhancers, B cells derived from mutant embryonic stem cells-in which both MiE(kappa) and 3'E-kappa were deleted on both kappa alleles-were analyzed for kappa rearrangement. Our findings indicate that these double-mutant B cells have essentially no kappa rearrangement but do rearrange and express lambda. Therefore, these two kappa enhancers share essential roles in activatingV(kappa)J(kappa) rearrangement. Our findings also indicate that the two kappa enhancers play overlapping and distinct roles in the demethylation of kappa in B cells.