Characteristics of Plasmablast Repertoire in Chronically HIV-Infected Individuals for Immunoglobulin H and L Chain Profiled by Single-Cell Analysis
Characteristics of Plasmablast Repertoire in Chronically HIV-Infected Individuals for Immunoglobulin H and L Chain Profiled by Single-Cell Analysis
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通过单细胞分析分析慢性 HIV 感染者免疫球蛋白 H 和 L 链的浆母细胞库特征
DOI：
10.3389/fimmu.2019.03163
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发表时间：
2020-02-11
影响因子：
7.3
通讯作者：
Zhang，Zhixin
中科院分区：
文献类型：
--
作者：
Liao，Hongyan;Li，Song;Zhang，Zhixin
多样化免疫球蛋白 (Ig) 库的表征可能有助于深入了解形成有效抗体 (Ab) 库的途径，以实现针对人类免疫缺陷病毒 (HIV) 感染的免疫反应。本研究旨在分析慢性 HIV 感染期间浆母细胞库的特征。通过单细胞 PCR 扩增来自先前接受过抗逆转录病毒治疗 (ART) 治疗的慢性 HIV 感染者 (HIVD) 和健康供者 (HD) 的浆母细胞的 Ig 可变区，为进一步的谱库分析奠定基础。我们比较了停止 ART 治疗后多种慢性 HIVD 患者和 HD 患者中表达的浆母细胞库。我们还检查了非生产性库，以确定重排机制的直接产物的指示，而不会影响 HIV 感染期间的选择。我们发现 HIVD 和 HD 受试者的生产性曲目之间存在多种差异，包括 HIVD 组中 VH 中 VH3-49、VH1-2、VH3-33、VH3-74 和 VH5-51 以及 D 片段中 D1-7、D1-14、D1-20 和 D5-5/18 的偏向使用，以及 CDRH3 区域中更短和优先的甘氨酸使用。还在轻链中检测到基因选择。值得注意的是，HIVD 和 HD 之间的生产性重排之间的差异超过了 HIVD 内部生产性和非生产性重排之间的差异。 HIV 感染可能对浆母细胞库的发育产生显着影响。选择的影响在塑造浆母细胞库方面意义有限。总体而言，数据表明浆母细胞生存的环境可以影响VH和VL基因在库中的分布以及表达的抗体的氨基酸组成。
Characterization of the diversified immunoglobulin (Ig) repertoire may provide insight into pathways that shape an efficient antibody (Ab) repertoire for immune response against human immunodeficiency virus (HIV) infection. This study aimed to profile characteristics of the plasmablast repertoire during chronic HIV infection. Ig variable regions of plasmablasts from both chronically HIV-infected donors (HIVDs) previously treated with antiretroviral therapy (ART) and healthy donors (HDs) were amplified by single-cell PCR to establish the basis for further repertoire analysis. We compared the plasmablast repertoires expressed in multiple chronically HIVDs after ART treatment cessation and HDs. We also examined the non-productive repertoire to identify the indication of the immediate products of the rearrangement machinery without an impact of selection during HIV infection. We found multiple differences between the productive repertoires of HIVD and HD subjects, including biased usages of VH3-49, VH1-2, VH3-33, VH3-74, and VH5-51 in VH and D1-7, D1-14, D1-20, and D5-5/18 in D segments in the HIVD group, as well as shorter and preferential glycine usages in CDRH3 regions. Gene selections were also detected in light chains. Notably, differences between productive rearrangements of HIVDs and HDs outnumbered those between productive and non-productive rearrangements within HIVDs. HIV infection may exert a dominant impact on the development of the plasmablast repertoire. The impact of selection is of limited significance in shaping the plasmablast repertoire. Overall, the data indicate that the environment in which the plasmablasts live can affect the distribution of the VH and VL genes in the repertoire and the amino acid compositions of the expressed Abs.