Characteristics of Plasmablast Repertoire in Chronically HIV-Infected Individuals for Immunoglobulin H and L Chain Profiled by Single-Cell Analysis

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 du...

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Main Authors: Hongyan Liao, Song Li, Yangsheng Yu, Yinshi Yue, Kaihong Su, Qin Zheng, Nenggang Jiang, Zhixin Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-02-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2019.03163/full
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author Hongyan Liao
Hongyan Liao
Song Li
Yangsheng Yu
Yinshi Yue
Kaihong Su
Kaihong Su
Kaihong Su
Qin Zheng
Nenggang Jiang
Zhixin Zhang
author_facet Hongyan Liao
Hongyan Liao
Song Li
Yangsheng Yu
Yinshi Yue
Kaihong Su
Kaihong Su
Kaihong Su
Qin Zheng
Nenggang Jiang
Zhixin Zhang
author_sort Hongyan Liao
collection DOAJ
description 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.
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spelling doaj.art-c0ba6fd7c7f144ae8be3c9b001dfe0172022-12-21T18:56:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-02-011010.3389/fimmu.2019.03163487478Characteristics of Plasmablast Repertoire in Chronically HIV-Infected Individuals for Immunoglobulin H and L Chain Profiled by Single-Cell AnalysisHongyan Liao0Hongyan Liao1Song Li2Yangsheng Yu3Yinshi Yue4Kaihong Su5Kaihong Su6Kaihong Su7Qin Zheng8Nenggang Jiang9Zhixin Zhang10Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, United StatesDepartment of Chemotherapy, Cancer Center, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, United StatesDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, United StatesDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, United StatesInternal Medicine, University of Nebraska Medical Center, Omaha, NE, United StatesEppley Research Institute, University of Nebraska Medical Center, Omaha, NE, United StatesDepartment of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, ChinaState Key Laboratory of Biotherapy, Ministry of Education Key Laboratory of Birth Defects, Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, ChinaCharacterization 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.03163/fullhuman immunodeficiency virusplasmablastrepertoirevariable regionsingle-cell PCR
spellingShingle Hongyan Liao
Hongyan Liao
Song Li
Yangsheng Yu
Yinshi Yue
Kaihong Su
Kaihong Su
Kaihong Su
Qin Zheng
Nenggang Jiang
Zhixin Zhang
Characteristics of Plasmablast Repertoire in Chronically HIV-Infected Individuals for Immunoglobulin H and L Chain Profiled by Single-Cell Analysis
Frontiers in Immunology
human immunodeficiency virus
plasmablast
repertoire
variable region
single-cell PCR
title Characteristics of Plasmablast Repertoire in Chronically HIV-Infected Individuals for Immunoglobulin H and L Chain Profiled by Single-Cell Analysis
title_full Characteristics of Plasmablast Repertoire in Chronically HIV-Infected Individuals for Immunoglobulin H and L Chain Profiled by Single-Cell Analysis
title_fullStr Characteristics of Plasmablast Repertoire in Chronically HIV-Infected Individuals for Immunoglobulin H and L Chain Profiled by Single-Cell Analysis
title_full_unstemmed Characteristics of Plasmablast Repertoire in Chronically HIV-Infected Individuals for Immunoglobulin H and L Chain Profiled by Single-Cell Analysis
title_short Characteristics of Plasmablast Repertoire in Chronically HIV-Infected Individuals for Immunoglobulin H and L Chain Profiled by Single-Cell Analysis
title_sort characteristics of plasmablast repertoire in chronically hiv infected individuals for immunoglobulin h and l chain profiled by single cell analysis
topic human immunodeficiency virus
plasmablast
repertoire
variable region
single-cell PCR
url https://www.frontiersin.org/article/10.3389/fimmu.2019.03163/full
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