Visualization of looping involving the immunoglobulin heavy-chain locus in developing B cells

Visualization of looping involving the immunoglobulin heavy-chain locus in developing B cells
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DOI:
10.1101/gad.1254305
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发表时间:
2005-02-01
影响因子:
10.5
通讯作者:
Murre, C
Murre, C
中科院分区:
生物学1区
文献类型:
--
作者:
Sayegh, C;Jhunjhunwala, S;Murre, C

文献摘要

被引文献

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免疫球蛋白重链(IgH)位点在准备进行IgH V(D)J重组的B细胞中发生大规模收缩。我们考虑了不同的IgH - V区环路在促进远程相互作用中起作用的可能性。在这里,我们同时可视化三个亚区域的IgH位点,使用三维荧光原位杂交。在B系和t系细胞中均观察到IgH位点内的环。然而,与造血祖细胞或CD8(+) t系细胞相比,在发育中的B细胞中检测到ighv区靠近ighdj簇的单等位基因环,其频率明显更高。虽然频率较低,但在rag缺乏的前b细胞中也观察到IgH V区域亚群的环化。基于这些观察结果,我们提出在IgH V(D)J重排之前,Ig基因座通过一个环机制重新定位,以促进Ig变量、多样性和连接片段的连接。
The immunoglobulin heavy-chain (IgH) locus undergoes large-scale contraction in B cells poised to undergo IgH V(D)J recombination. We considered the possibility that looping of distinct IgH V regions plays a role in promoting long-range interactions. Here, we simultaneously visualize three subregions of the IgH locus, using three-dimensional fluorescence in situ hybridization. Looping within the IgH locus was observed in both B- and T-lineage cells. However, monoallelic looping of IgH V regions into close proximity of the IgH DJ cluster was detected in developing B cells with significantly higher frequency when compared with hematopoietic progenitor or CD8(+) T-lineage cells. Looping of a subset of IgH V regions, albeit at lower frequency, was also observed in RAG-deficient pro-B cells. Based on these observations, we propose that Ig loci are repositioned by a looping mechanism prior to IgH V(D)J rearrangement to facilitate the joining of Ig variable, diversity, and joining segments.