Germinal center B-cell-associated DNA hypomethylation at transcriptional regions of the AID gene
Germinal center B-cell-associated DNA hypomethylation at transcriptional regions of the AID gene
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DOI：
10.1016/j.molimm.2007.09.023
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发表时间：
2008-03-01
影响因子：
3.6
通讯作者：
Sakaguchi, Nobuo
中科院分区：
文献类型：
--
作者：
Fujimura, Satoru;Matsui, Takeshi;Sakaguchi, Nobuo
t细胞依赖抗原诱导外周血淋巴滤泡生发中心b细胞分化。我们通过检测小鼠AID转录的调控区域研究了GC b细胞分化是否与DNA甲基化状态相关，这些区域对b细胞成熟至关重要。前B细胞、未成熟B细胞、成熟B细胞、浆细胞瘤或T细胞的艾滋病阴性细胞系在5'-启动子区和含子区表现出不同的高甲基化谱。相反，艾滋病阳性gc型B细胞在这些区域低甲基化。用脂多糖和白介素-4刺激脾B细胞导致5'-启动子和内含子CpG位点的DNA低甲基化，这与AID转录的增加成正比。成熟的GL7(+)Fas(+) GC B细胞在这些CpG位点低甲基化，特别是在pax5共识位点和内含子位点附近。然而，Syndecan-1（+）浆细胞显示DNA高甲基化，如浆细胞瘤中所见。转录调控区的甲基化状态可能有助于GC b细胞分化过程中AID转录的阶段依赖性激活。(c) 2007 Elsevier Ltd.版权所有。
T-cell-dependent antigen induces differentiation of germinal center (GC) B-cell in peripheral lymphoid follicles. We studied whether GC B-cell differentiation is associated with DNA methylation status by examining regulatory regions of mouse AID transcription that are essential for B-cell maturation. AID-negative cell lines of pre-B cells, immature B cells, mature B cells, plasmacytomas or T cells showed various hypermethylation profiles in the 5'-promoter and intronic regions. In contrast, AID-positive GC-type B cells were hypomethylated in these regions. Stimulation of splenic B cells with lipopolysaccharide and interleukin-4 caused DNA hypornethylation in the 5'-promoter and intronic CpG sites proportional to the increase in AID transcription. Mature GL7(+)Fas(+) GC B cells were hypomethylated at these CpG sites, especially near the Pax5-consensus site and an intronic site. However, Syndecan-1(+) plasma cells showed DNA hypermethylation, as seen in plasmacytomas. Methylation status of the transcriptional regulatory region might contribute to stage-dependent activation of AID transcription during GC B-cell differentiation. (c) 2007 Elsevier Ltd. All rights reserved.