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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Frequency and genetic characterization of V(DD)J recombinants in the human peripheral blood antibody repertoire
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Frequency and genetic characterization of V(DD)J recombinants in the human peripheral blood antibody repertoire

机译：人类外周血抗体库中V（DD）J重组子的频率和遗传特征

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摘要

Antibody heavy-chain recombination that results in the incorporation of multiple diversity (D) genes, although uncommon, contributes substantially to the diversity of the human antibody repertoire. Such recombination allows the generation of heavy chain complementarity determining region 3 (HCDR3) regions of extreme length and enables junctional regions that, because of the nucleotide bias of N-addition regions, are difficult to produce through normal V(D)J recombination. Although this non-classical recombination process has been observed infrequently, comprehensive analysis of the frequency and genetic characteristics of such events in the human peripheral blood antibody repertoire has not been possible because of the rarity of such recombinants and the limitations of traditional sequencing technologies. Here, through the use of high-throughput sequencing of the normal human peripheral blood antibody repertoire, we analysed the frequency and genetic characteristics of V(DD)J recombinants. We found that these recombinations were present in approximately 1 in 800 circulating B cells, and that the frequency was severely reduced in memory cell subsets. We also found that V(DD)J recombination can occur across the spectrum of diversity genes, indicating that virtually all recombination signal sequences that flank diversity genes are amenable to V(DD)J recombination. Finally, we observed a repertoire bias in the diversity gene repertoire at the upstream (5′) position, and discovered that this bias was primarily attributable to the order of diversity genes in the genomic locus.
机译：抗体重链重组虽然不常见，但却导致多个多样性（D）基因的掺入，在很大程度上有助于人类抗体库的多样性。这样的重组允许产生极端长度的重链互补决定区3（HCDR3）区，并且使得由于N-加成区的核苷酸偏向而难以通过正常的V（D）J重组产生的连接区成为可能。尽管很少观察到这种非经典的重组过程，但由于此类重组子的稀有性和传统测序技术的局限性，因此无法对人外周血抗体库中此类事件的频率和遗传特性进行全面分析。在这里，通过使用正常人外周血抗体库的高通量测序，我们分析了V（DD）J重组子的频率和遗传特性。我们发现这些重组存在于800个循环B细胞中的大约1个中，并且频率在记忆细胞亚群中大大降低。我们还发现，V（DD）J重组可在多样性基因的整个谱图中发生，这表明侧翼多样性基因的几乎所有重组信号序列都适合V（DD）J重组。最后，我们在上游（5'）位置观察到多样性基因库中的库偏差，并发现这种偏差主要归因于基因组基因座中多样性基因的顺序。

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