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Aberrant B cell repertoire selection associated with HIV neutralizing antibody breadth
Nature Immunology ( IF 30.5 ) Pub Date : 2020-01-20 , DOI: 10.1038/s41590-019-0581-0
Krishna M Roskin 1, 2, 3 , Katherine J L Jackson 4 , Ji-Yeun Lee 5 , Ramona A Hoh 5 , Shilpa A Joshi 5 , Kwan-Ki Hwang 6 , Mattia Bonsignori 6 , Isabela Pedroza-Pacheco 7 , Hua-Xin Liao 6 , M Anthony Moody 6 , Andrew Z Fire 5, 8 , Persephone Borrow 7 , Barton F Haynes 6, 9, 10, 11 , Scott D Boyd 5
Affiliation  

A goal of HIV vaccine development is to elicit antibodies with neutralizing breadth. Broadly neutralizing antibodies (bNAbs) to HIV often have unusual sequences with long heavy-chain complementarity-determining region loops, high somatic mutation rates and polyreactivity. A subset of HIV-infected individuals develops such antibodies, but it is unclear whether this reflects systematic differences in their antibody repertoires or is a consequence of rare stochastic events involving individual clones. We sequenced antibody heavy-chain repertoires in a large cohort of HIV-infected individuals with bNAb responses or no neutralization breadth and uninfected controls, identifying consistent features of bNAb repertoires, encompassing thousands of B cell clones per individual, with correlated T cell phenotypes. These repertoire features were not observed during chronic cytomegalovirus infection in an independent cohort. Our data indicate that the development of numerous B cell lineages with antibody features associated with autoreactivity may be a key aspect in the development of HIV neutralizing antibody breadth.



中文翻译:

与 HIV 中和抗体广度相关的异常 B 细胞库选择

HIV 疫苗开发的一个目标是引发具有中和广度的抗体。针对 HIV 的广泛中和抗体 (bNAb) 通常具有不寻常的序列,具有长的重链互补决定区环、高体细胞突变率和多反应性。一部分 HIV 感染者会产生这种抗体,但尚不清楚这是否反映了他们抗体库的系统差异,或者是涉及个体克隆的罕见随机事件的结果。我们在一大群具有 bNAb 反应或没有中和广度和未感染对照的 HIV 感染个体中对抗体重链库进行了测序,确定了 bNAb 库的一致特征,包括每个个体数千个 B 细胞克隆,具有相关的 T 细胞表型。在独立队列的慢性巨细胞病毒感染期间未观察到这些特征。我们的数据表明,具有与自身反应性相关的抗体特征的众多 B 细胞谱系的发展可能是 HIV 中和抗体广度发展的关键方面。

更新日期:2020-01-20
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