Genetic variation in the immunoglobulin heavy chain locus shapes the human antibody repertoire.
Genetic variation in the immunoglobulin heavy chain locus shapes the human antibody repertoire.
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DOI：
10.1038/s41467-023-40070-x
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发表时间：
2023-07-21
影响因子：
16.6
通讯作者：
Watson, Corey T.
中科院分区：
文献类型：
--
作者：
Rodriguez, Oscar L.;Safonova, Yana;Silver, Catherine A.;Shields, Kaitlyn;Gibson, William S.;Kos, Justin T.;Tieri, David;Ke, Hanzhong;Jackson, Katherine J. L.;Boyd, Scott D.;Smith, Melissa L.;Marasco, Wayne A.;Watson, Corey T.
抗体应答的变化与疾病的不同结局以及次优疫苗和治疗应答有关，其决定因素尚未完全阐明。对抗模型，假设抗体主要是由随机过程产生的，我们证明了免疫球蛋白重链基因座（IGH）内的多态性影响幼稚和抗原经验丰富的抗体库，表明遗传学倾向于个人安装定性和定量不同的抗体反应。我们将最近开发的长读基因组测序方法与抗体谱分析相结合，以全面解决IGH遗传变异，包括新的结构变异，单核苷酸变异以及基因和等位基因。我们发现IGH种系变异决定了抗体基因在表达谱中的存在和频率，包括那些富含与V（D）J重组相关的功能元件的基因，以及重叠的疾病相关变异。这些结果阐明了利用IGH遗传学的力量，以更好地了解疾病中抗体反应的调节，功能和动力学。人免疫球蛋白重链（IGH）基因座的单倍型多样性特征不明显。在这里，作者使用长读测序来发现广泛的IGH多样性，并将种系变异与抗体库中的变异联系起来。
Variation in the antibody response has been linked to differential outcomes in disease, and suboptimal vaccine and therapeutic responsiveness, the determinants of which have not been fully elucidated. Countering models that presume antibodies are generated largely by stochastic processes, we demonstrate that polymorphisms within the immunoglobulin heavy chain locus (IGH) impact the naive and antigen-experienced antibody repertoire, indicating that genetics predisposes individuals to mount qualitatively and quantitatively different antibody responses. We pair recently developed long-read genomic sequencing methods with antibody repertoire profiling to comprehensively resolve IGH genetic variation, including novel structural variants, single nucleotide variants, and genes and alleles. We show that IGH germline variants determine the presence and frequency of antibody genes in the expressed repertoire, including those enriched in functional elements linked to V(D)J recombination, and overlapping disease-associated variants. These results illuminate the power of leveraging IGH genetics to better understand the regulation, function, and dynamics of the antibody response in disease. Haplotype diversity in the human immunoglobulin heavy chain (IGH) locus is poorly characterized. Here, the authors use long-read sequencing to discover extensive IGH diversity and link germline variants to variation in the antibody repertoire.
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影响因子：
64.8
作者：
Boix CA;James BT;Park YP;Meuleman W;Kellis M
通讯作者：
Kellis M
通过多焦点基因型聚类检测人口结构。
影响因子：
2.9
作者：
Gao, Xiaoyi;Starmer, Joshua
通讯作者：
Starmer, Joshua
影响因子：
64.8
作者：
Ba Z;Lou J;Ye AY;Dai HQ;Dring EW;Lin SG;Jain S;Kyritsis N;Kieffer-Kwon KR;Casellas R;Alt FW
通讯作者：
Alt FW
影响因子：
9.8
作者：
Browning, Brian L.;Zhou, Ying;Browning, Sharon R.
通讯作者：
Browning, Sharon R.
影响因子：
16.6
作者：
Bhat, Khalid H.;Priyadarshi, Saurabh;Naiyer, Sarah;Qu, Xinyan;Farooq, Hammad;Kleiman, Eden;Xu, Jeffery;Lei, Xue;Cantillo, Jose F.;Wuerffel, Robert;Baumgarth, Nicole;Liang, Jie;Feeney, Ann J.;Kenter, Amy L.
通讯作者：
Kenter, Amy L.