前B细胞中免疫球蛋白κ基因座的多样化转录激活有助于轻链表达的等位基因排斥。

Variegated transcriptional activation of the immunoglobulin kappa locus in pre-b cells contributes to the allelic exclusion of light-chain expression.

作者信息

Liang Hong-Erh, Hsu Lih-Yun, Cado Dragana, Schlissel Mark S

机构信息

Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.

出版信息

Cell. 2004 Jul 9;118(1):19-29. doi: 10.1016/j.cell.2004.06.019.

DOI:10.1016/j.cell.2004.06.019

PMID:15242641

Abstract

Regulated gene rearrangement is thought to underlie allelic exclusion, the observation that an individual B cell expresses only a single immunoglobulin molecule. Previous data has implicated transcriptional activation of rearranging loci in the regulation of their accessibility to the V(D)J recombinase. Using homologous recombination in ES cells, we have generated "knockin" mice which express a GFP cDNA from an unrearranged immunoglobulin kappa light-chain allele. Surprisingly, we find that only a small fraction of kappa alleles are highly transcribed in a population of pre-B cells, that such transcription is monoallelic, and that these highly transcribed alleles account for the vast majority of kappa light-chain gene rearrangement. These data lead us to suggest that probabilistic enhancer activation and allelic competition are part of the mechanism of kappa locus allelic exclusion and may be a general mechanism contributing to cellular differentiation during development.

摘要

调控基因重排被认为是等位基因排斥的基础，即观察到单个B细胞仅表达单个免疫球蛋白分子。先前的数据表明，重排基因座的转录激活在调节其对V(D)J重组酶的可及性中起作用。利用胚胎干细胞中的同源重组，我们构建了“敲入”小鼠，其从未重排的免疫球蛋白κ轻链等位基因表达绿色荧光蛋白cDNA。令人惊讶的是，我们发现在前B细胞群体中，只有一小部分κ等位基因被高度转录，这种转录是单等位基因的，并且这些高度转录的等位基因占κ轻链基因重排的绝大多数。这些数据使我们提出，概率性增强子激活和等位基因竞争是κ基因座等位基因排斥机制的一部分，并且可能是发育过程中细胞分化的一种普遍机制。