Cedar Howard, Bergman Yehudit
Department of Cellular Biochemistry and Human Genetics, Hebrew University Medical School, Jerusalem 91120, Israel.
Curr Opin Immunol. 2008 Jun;20(3):308-17. doi: 10.1016/j.coi.2008.02.002. Epub 2008 Apr 9.
Allelic exclusion guarantees that each B or T cell only produces a single antigen receptor, and in this way contributes to immune diversity. This process is actually initiated in the early embryo when the immune receptor loci become asynchronously replicating in a stochastic manner with one early and one late allele in each cell. This distinct differential replication timing feature then serves an instructive mark that directs a series of allele-specific epigenetic events in the immune system, including programmed histone modification, nuclear localization and DNA demethylation that ultimately bring about preferred rearrangement on a single allele, and this decision is temporally stabilized by feedback mechanisms that inhibit recombination on the second allele. In principle, these same molecular components are also used for controlling monoallelic expression at other genomic loci, such as those carrying interleukins and olfactory receptor genes that require the choice of one gene out of a large array. Thus, allelic exclusion appears to represent a general epigenetic phenomenon that is modeled on the same basis as X chromosome inactivation.
等位基因排斥确保每个B细胞或T细胞仅产生单一抗原受体，以此促进免疫多样性。这一过程实际上始于胚胎早期，此时免疫受体基因座以随机方式进行异步复制，每个细胞中有一个早期等位基因和一个晚期等位基因。这种独特的差异复制时间特征随后成为一种指导性标记，引导免疫系统中一系列等位基因特异性的表观遗传事件，包括程序性组蛋白修饰、核定位和DNA去甲基化，最终导致单个等位基因上的优先重排，并且这一决定通过抑制第二个等位基因重组的反馈机制在时间上得以稳定。原则上，这些相同的分子成分也用于控制其他基因组位点的单等位基因表达，例如那些携带白细胞介素和嗅觉受体基因的位点，这些基因需要从大量基因中选择一个。因此，等位基因排斥似乎代表了一种普遍的表观遗传现象，其模式与X染色体失活相同。
