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AID 驱动的缺失导致 B 细胞中免疫球蛋白重链基因座自杀重组。

AID-driven deletion causes immunoglobulin heavy chain locus suicide recombination in B cells.

机构信息

Limoges University, CNRS, 2 rue Marcland, 87025 Limoges Cedex, France.

出版信息

Science. 2012 May 18;336(6083):931-4. doi: 10.1126/science.1218692. Epub 2012 Apr 26.

DOI:10.1126/science.1218692
PMID:22539552
Abstract

Remodeling of immunoglobulin genes by activation-induced deaminase (AID) is required for affinity maturation and class-switch recombination in mature B lymphocytes. In the immunoglobulin heavy chain locus, these processes are predominantly controlled by the 3' cis-regulatory region. We now show that this region is transcribed and undergoes AID-mediated mutation and recombination around phylogenetically conserved switchlike DNA repeats. Such recombination, which we term locus suicide recombination, deletes the whole constant region gene cluster and thus stops expression of the immunoglobulin of the B cell surface, which is critical for B cell survival. The frequency of this event is approaching that of class switching and makes it a potential regulator of B cell homeostasis.

摘要

免疫球蛋白基因的重排是由激活诱导的脱氨酶(AID)介导的,这是成熟 B 淋巴细胞中亲和力成熟和类别转换重组所必需的。在免疫球蛋白重链基因座中,这些过程主要受 3'顺式调控区控制。我们现在表明,这个区域是转录的,并在进化上保守的开关样 DNA 重复周围发生 AID 介导的突变和重组。这种重组,我们称之为基因座自杀重组,删除了整个恒定区基因簇,从而停止了 B 细胞表面免疫球蛋白的表达,这对 B 细胞的存活至关重要。这种事件的频率接近类别转换的频率,使其成为 B 细胞内稳态的潜在调节剂。

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