Lineage structure of the human antibody repertoire in response to influenza vaccination.
Lineage structure of the human antibody repertoire in response to influenza vaccination.
复制标题
DOI：
10.1126/scitranslmed.3004794
复制
发表时间：
2013-02-06
影响因子：
17.1
通讯作者：
Quake SR
中科院分区：
文献类型：
--
作者：
Jiang N;He J;Weinstein JA;Penland L;Sasaki S;He XS;Dekker CL;Zheng NY;Huang M;Sullivan M;Wilson PC;Greenberg HB;Davis MM;Fisher DS;Quake SR
人类抗体库是抵御传染病的最重要防御手段之一，疫苗的研发使得能够针对特定病原体提供靶向保护。然而，测量和分析免疫球蛋白序列库存在诸多挑战，例如每个B细胞在其基因组中包含独特的抗体序列，抗体库不是恒定的而是随时间变化，以及抗体序列之间的高度相似性。我们通过使用高通量长读长测序在流感疫苗接种的背景下对表达的人类抗体库进行免疫基因组学表征来应对这一挑战。对来自健康个体的500万个抗体重链序列进行的信息学分析使我们能够对同种型分布进行全面表征，确定库的谱系结构，并测量与年龄和抗原相关的突变活性。我们对个体库的克隆结构和突变分布的分析表明，老年受试者的谱系数量减少，但在接种疫苗前其库中的突变负荷增加，并且其中一些受试者的库具有寡克隆特征，即与年轻受试者相比，其谱系的多样性大大降低。因此，我们已经表明，对免疫系统克隆结构的全面分析可直接深入了解疫苗接种的效果，并提供与年龄相关影响的详细分子画像。
The human antibody repertoire is one of the most important defenses against infectious disease, and the development of vaccines has enabled the conferral of targeted protection to specific pathogens. However, there are many challenges to measuring and analyzing the immunoglobulin sequence repertoire, such as the fact that each B cell contains a distinct antibody sequence encoded in its genome, that the antibody repertoire is not constant but changes over time, and the high similarity between antibody sequences. We have addressed this challenge by using high-throughput long read sequencing to perform immunogenomic characterization of expressed human antibody repertoires in the context of influenza vaccination. Informatic analysis of 5 million antibody heavy chain sequences from healthy individuals allowed us to perform global characterizations of isotype distributions, determine the lineage structure of the repertoire and measure age and antigen related mutational activity. Our analysis of the clonal structure and mutational distribution of individuals’ repertoires shows that elderly subjects have a decreased number of lineages but an increased pre-vaccination mutation load in their repertoire and that some of these subjects have an oligoclonal character to their repertoire in which the diversity of the lineages is greatly reduced relative to younger subjects. We have thus shown that global analysis of the immune system’s clonal structure provides direct insight into the effects of vaccination and provides a detailed molecular portrait of age-related effects.
登录
查看更多内容
DOI：
10.4049/jimmunol.1101823
发表时间：
2011-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Krause JC;Tsibane T;Tumpey TM;Huffman CJ;Briney BS;Smith SA;Basler CF;Crowe JE Jr
通讯作者：
Crowe JE Jr
影响因子：
64.8
作者：
Wrammert, Jens;Smith, Kenneth;Wilson, Patrick C.
通讯作者：
Wilson, Patrick C.
影响因子：
15.9
作者：
Sasaki, Sanae;Sullivan, Meghan;He, Xiao-Song
通讯作者：
He, Xiao-Song
影响因子：
46.9
作者：
Reddy, Sai T.;Ge, Xin;Georgiou, George
通讯作者：
Georgiou, George
影响因子：
64.8
作者：
Yan, Catherine T.;Boboila, Cristian;Alt, Frederick W.
通讯作者：
Alt, Frederick W.