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Nuclear positioning rather than contraction controls ordered rearrangements of immunoglobulin loci

机译:核定位而不是收缩控制免疫球蛋白基因素的有序重排

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Progenitor-B cells recombine their immunoglobulin (Ig) loci to create unique antigen receptors. Despite a common recombination machinery, the Ig heavy and Ig light chain loci rearrange in a stepwise manner. We studied pre-pro-B cells and Rag(-/-) progenitor-B cells to determine whether Ig locus contraction or nuclear positioning is decisive for stepwise rearrangements. We found that both Ig loci were contracted in pro-B and pre-B cells. Ig kappa relocated from the nuclear lamina to central domains only at the proB cell stage, whereas, Ig. remained sequestered at the lamina, and only at the pre-B cell stage located to central nuclear domains. Finally, in vitro induced re-positioning of Ig alleles away from the nuclear periphery increased germline transcription of Ig loci in pre-pro-B cells. Thus, Ig locus contraction juxtaposes genomically distant elements to mediate efficient recombination, however, sequential positioning of Ig loci away from the nuclear periphery determines stage-specific accessibility of Ig loci.
机译:祖母B细胞重新组合其免疫球蛋白(Ig)基因座以产生独特的抗原受体。尽管具有常见的重组机械,但IG重和IG轻链基因座以逐步的方式重新排列。我们研究了Pre-B细胞和RAG( - / - )祖细胞的预释放液,以确定Ig轨迹收缩或核定位是否对逐步重排进行决定性。我们发现两个Ig基因座在Pro-B和B前细胞中收缩。 Ig Kappa仅在核细胞阶段从核薄片到中央结构域,而Ig。保持在椎板上被隔离,并且仅在位于中央核结构域的前B细胞阶段。最后,体外诱导IG等位基因远离Pre-B细胞中Ig基因座的核外周增加的核外围增加。因此,Ig轨迹收缩对基因组远处元素并置以介导有效的重组,然而,IG基因座远离核外周的顺序定位决定了IG基因座的阶段特异性可接近性。

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