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异常的B细胞库选择与HIV中和抗体广度有关
作者:小柯机器人 发布时间:2020/1/25 10:53:40

美国斯坦福大学Scott D. Boyd、杜克大学医学院Barton F. Haynes等研究人员合作发现,异常的B细胞库选择与HIV中和抗体广度有关。该研究于2020年1月20日在线发表于国际一流学术期刊《自然—免疫学》。

研究人员对一大批受HIV感染个体的抗体重链库进行了测序,这些个体具有广泛中和抗体(bNAb)反应或无中和广度以及未感染的对照,从而确定了bNAb库的一致特征,包括每个人数千个B细胞克隆,以及相关的T细胞表型。在一个独立的队列中,慢性巨细胞病毒感染期间未观察到这些库特征。这些数据表明,众多具有自身反应性相关抗体特征B细胞谱系的发展可能是HIV中和抗体广度发展的关键。
 
据了解,HIV疫苗开发的目标是引发具有中和广度的抗体。针对HIV的bNAb通常具有不寻常的序列,即具有长的重链互补决定区环、高的体细胞突变率和多反应性。一部分受HIV感染的个体会产生此类抗体,但尚不清楚这是否反映了其抗体库中的系统差异,还是由于涉及单个克隆的罕见随机事件的结果。
 
附:英文原文

Title: Aberrant B cell repertoire selection associated with HIV neutralizing antibody breadth

Author: Krishna M. Roskin, Katherine J. L. Jackson, Ji-Yeun Lee, Ramona A. Hoh, Shilpa A. Joshi, Kwan-Ki Hwang, Mattia Bonsignori, Isabela Pedroza-Pacheco, Hua-Xin Liao, M. Anthony Moody, Andrew Z. Fire, Persephone Borrow, Barton F. Haynes, Scott D. Boyd

Issue&Volume: 2020-01-20

Abstract: 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.

DOI: 10.1038/s41590-019-0581-0

Source: https://www.nature.com/articles/s41590-019-0581-0

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex