In-Depth Analysis of Human Neonatal and Adult IgM Antibody Repertoires.
In-Depth Analysis of Human Neonatal and Adult IgM Antibody Repertoires.
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DOI：
10.3389/fimmu.2018.00128
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发表时间：
2018
影响因子：
7.3
通讯作者：
Ying T
中科院分区：
文献类型：
--
作者：
Hong B;Wu Y;Li W;Wang X;Wen Y;Jiang S;Dimitrov DS;Ying T
尽管高通量测序和相关的生物信息学技术已经能够对人类免疫库进行深入的、基于序列的表征，但只有少数针对相对较少序列的研究探索了新生儿抗体库的特征，结论相互矛盾。为了更全面地了解人类IgM抗体库，我们对新生儿脐带血（CB）和健康成人外周血（HH）的B淋巴细胞的IgM重链库进行了Illumina测序和IMGT/HighV-QUEST分析。比较研究意外地揭示了新生儿和成人曲目之间的高度相似性。在这两个基因库中，VDJ基因的使用没有显著差异，使用频率最高的VDJ基因是IGHV4-59、IGHD3-10和IGHJ3。CDR1 （CB: 8.5, HH: 8.4）和CDR2 （CB: 7.6, HH: 7.5）的平均氨基酸（aa）长度以及CDR3的aa组成和平均疏水性在两个储备间无显著差异。然而，CDR3在HH库中的平均aa长度比CB库长（CB: 14.5, HH: 15.5）。此外，HH库中CDR1 （CB: 19.33%, HH: 25.84%）和CDR2 （CB: 9.26%, HH: 17.82%）的aa突变频率高于CB库。有趣的是，这两个基因库之间最显著的差异是N2添加的发生（CB: 64.87%, HH: 85.69%），这一过程发生在V-D-J重组过程中，在D-和j基因片段之间引入随机核苷酸添加。健康成人的抗体库比新生儿更多样化，这主要是由于N2添加的发生率更高。这些发现可能有助于更好地了解抗体的发展和进化途径，并可能对促进产生更有效的抗体疗法和疫苗具有潜在的实用价值。
Although high-throughput sequencing and associated bioinformatics technologies have enabled the in-depth, sequence-based characterization of human immune repertoires, only a few studies on a relatively small number of sequences explored the characteristics of antibody repertoires in neonates, with contradictory conclusions. To gain a more comprehensive understanding of the human IgM antibody repertoire, we performed Illumina sequencing and IMGT/HighV-QUEST analysis of IgM heavy chain repertoire of the B lymphocytes from the cord blood (CB) of neonates, as well as the repertoire from peripheral blood of healthy human adults (HH). The comparative study revealed unexpectedly high levels of similarity between the neonatal and adult repertoires. In both repertoires, the VDJ gene usage showed no significant difference, and the most frequently used VDJ gene was IGHV4-59, IGHD3-10, and IGHJ3. The average amino acid (aa) length of CDR1 (CB: 8.5, HH: 8.4) and CDR2 (CB: 7.6, HH: 7.5), as well as the aa composition and the average hydrophobicity of the CDR3 demonstrated no significant difference between the two repertories. However, the average aa length of CDR3 was longer in the HH repertoire than the CB repertoire (CB: 14.5, HH: 15.5). Besides, the frequencies of aa mutations in CDR1 (CB: 19.33%, HH: 25.84%) and CDR2 (CB: 9.26%, HH: 17.82%) were higher in the HH repertoire compared to the CB repertoire. Interestingly, the most prominent difference between the two repertoires was the occurrence of N2 addition (CB: 64.87%, HH: 85.69%), a process that occurs during V-D-J recombination for introducing random nucleotide additions between D- and J-gene segments. The antibody repertoire of healthy adults was more diverse than that of neonates largely due to the higher occurrence of N2 addition. These findings may lead to a better understanding of antibody development and evolution pathways and may have potential practical value for facilitating the generation of more effective antibody therapeutics and vaccines.