Daly Janssen, Licence Steve, Nanou Aikaterini, Morgan Geoff, Mårtensson Inga-Lill
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.
EMBO J. 2007 Oct 3;26(19):4273-82. doi: 10.1038/sj.emboj.7601846. Epub 2007 Sep 6.
The process of allelic exclusion ensures that each B cell expresses a B-cell receptor encoded by only one of its Ig heavy (IgH) and light (IgL) chain alleles. Although its precise mechanism is unknown, recruitment of the nonfunctional IgH allele to centromeric heterochromatin correlates with the establishment of allelic exclusion. Similarly, recruitment in activated splenic B cells correlates with cell division. In the latter, the recruited IgH allele was reported to be transcriptionally silent. However, it is not known whether monoallelic recruitment during establishment of allelic exclusion correlates with transcriptional silencing. To investigate this, we assessed the transcriptional status of both IgH alleles in single primary cells over the course of B-cell development, using RNA fluorescence in situ hybridization. Before allelic exclusion both alleles are transcribed. Thereafter, in pre-BII and subsequent developmental stages both functional and nonfunctional VDJ- and DJ-transcription is observed. Thus, after the establishment of IgH allelic exclusion, monoallelic recruitment to heterochromatin does not silence VDJ- or DJ-transcription, but serves another purpose.
等位基因排斥过程确保每个B细胞仅表达由其一条Ig重链（IgH）和轻链（IgL）等位基因编码的B细胞受体。尽管其确切机制尚不清楚，但将无功能的IgH等位基因募集到着丝粒异染色质与等位基因排斥的建立相关。同样，在活化的脾B细胞中的募集与细胞分裂相关。在后者中，据报道被募集的IgH等位基因转录沉默。然而，尚不清楚在等位基因排斥建立过程中的单等位基因募集是否与转录沉默相关。为了研究这一点，我们使用RNA荧光原位杂交评估了单个原代细胞在B细胞发育过程中两个IgH等位基因的转录状态。在等位基因排斥之前，两个等位基因都被转录。此后，在前BII细胞及后续发育阶段，观察到功能性和非功能性的VDJ和DJ转录。因此，在IgH等位基因排斥建立后，单等位基因募集到异染色质不会使VDJ或DJ转录沉默，而是另有作用。
