Circulating Plasmablasts from Chronically Human Immunodeficiency Virus-Infected Individuals Predominantly Produce Polyreactive/Autoreactive Antibodies

Understanding the B-cell response during chronic human immunodeficiency virus (HIV) infection is essential for eliciting broad and potent neutralizing antibodies (Abs). In this study, we analyzed the plasmablast repertoire of chronically HIV-infected individuals in combination with antiretroviral th...

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Main Authors: Hongyan Liao, Yangsheng Yu, Song Li, Yinshi Yue, Chuanmin Tao, Kaihong Su, Zhixin Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-12-01
Series:Frontiers in Immunology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fimmu.2017.01691/full
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author Hongyan Liao
Hongyan Liao
Yangsheng Yu
Song Li
Song Li
Yinshi Yue
Chuanmin Tao
Kaihong Su
Kaihong Su
Kaihong Su
Zhixin Zhang
Zhixin Zhang
author_facet Hongyan Liao
Hongyan Liao
Yangsheng Yu
Song Li
Song Li
Yinshi Yue
Chuanmin Tao
Kaihong Su
Kaihong Su
Kaihong Su
Zhixin Zhang
Zhixin Zhang
author_sort Hongyan Liao
collection DOAJ
description Understanding the B-cell response during chronic human immunodeficiency virus (HIV) infection is essential for eliciting broad and potent neutralizing antibodies (Abs). In this study, we analyzed the plasmablast repertoire of chronically HIV-infected individuals in combination with antiretroviral therapy (ART). Among the obtained 72 recombinant monoclonal antibodies (mAbs), 27.8% weakly bound to HIV gp140 and were non-neutralizing. Remarkably, 56.9% were polyreactive and 55.6% were autoreactive. The prominent feature of being polyreactive/autoreactive is not limited to anti-gp140 Abs. Furthermore, these polyreactive/autoreactive Abs displayed striking cross-reactivity with DWEYS in the N-methyl-d-aspartate receptor (NMDAR), and this binding induced SH-SY5Y cell apoptosis. We also found higher frequencies of VH4-34 utilization and VH replacement in the plasmablast repertoire of chronically HIV-infected individuals, which may contribute to the generation of poly/autoreactive Abs. Taken together, these data demonstrate that circulating plasmablasts in chronically HIV-infected individuals experienced with ART predominantly produce poly/autoreactive Abs with minimal anti-HIV neutralizing capacity and potential cross-reactivity with autoantigens. This may represent another dysfunction of B cells during chronic HIV infection.
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spelling doaj.art-e05f9ae1191e4cdd8cafde4c101aa1172022-12-21T17:32:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-12-01810.3389/fimmu.2017.01691305075Circulating Plasmablasts from Chronically Human Immunodeficiency Virus-Infected Individuals Predominantly Produce Polyreactive/Autoreactive AntibodiesHongyan Liao0Hongyan Liao1Yangsheng Yu2Song Li3Song Li4Yinshi Yue5Chuanmin Tao6Kaihong Su7Kaihong Su8Kaihong Su9Zhixin Zhang10Zhixin Zhang11Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 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 StatesQilu Hospital of Shandong University, Jinan, ChinaDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, United StatesDepartment of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment 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 Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, United StatesDepartment of Pediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy, Ministry of Education Key Laboratory of Birth Defects, Sichuan University, Chengdu, ChinaUnderstanding the B-cell response during chronic human immunodeficiency virus (HIV) infection is essential for eliciting broad and potent neutralizing antibodies (Abs). In this study, we analyzed the plasmablast repertoire of chronically HIV-infected individuals in combination with antiretroviral therapy (ART). Among the obtained 72 recombinant monoclonal antibodies (mAbs), 27.8% weakly bound to HIV gp140 and were non-neutralizing. Remarkably, 56.9% were polyreactive and 55.6% were autoreactive. The prominent feature of being polyreactive/autoreactive is not limited to anti-gp140 Abs. Furthermore, these polyreactive/autoreactive Abs displayed striking cross-reactivity with DWEYS in the N-methyl-d-aspartate receptor (NMDAR), and this binding induced SH-SY5Y cell apoptosis. We also found higher frequencies of VH4-34 utilization and VH replacement in the plasmablast repertoire of chronically HIV-infected individuals, which may contribute to the generation of poly/autoreactive Abs. Taken together, these data demonstrate that circulating plasmablasts in chronically HIV-infected individuals experienced with ART predominantly produce poly/autoreactive Abs with minimal anti-HIV neutralizing capacity and potential cross-reactivity with autoantigens. This may represent another dysfunction of B cells during chronic HIV infection.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01691/fullhuman immunodeficiency virusB cellplasmablastpolyreactive antibodyautoreactive antibodyIg heavy
spellingShingle Hongyan Liao
Hongyan Liao
Yangsheng Yu
Song Li
Song Li
Yinshi Yue
Chuanmin Tao
Kaihong Su
Kaihong Su
Kaihong Su
Zhixin Zhang
Zhixin Zhang
Circulating Plasmablasts from Chronically Human Immunodeficiency Virus-Infected Individuals Predominantly Produce Polyreactive/Autoreactive Antibodies
Frontiers in Immunology
human immunodeficiency virus
B cell
plasmablast
polyreactive antibody
autoreactive antibody
Ig heavy
title Circulating Plasmablasts from Chronically Human Immunodeficiency Virus-Infected Individuals Predominantly Produce Polyreactive/Autoreactive Antibodies
title_full Circulating Plasmablasts from Chronically Human Immunodeficiency Virus-Infected Individuals Predominantly Produce Polyreactive/Autoreactive Antibodies
title_fullStr Circulating Plasmablasts from Chronically Human Immunodeficiency Virus-Infected Individuals Predominantly Produce Polyreactive/Autoreactive Antibodies
title_full_unstemmed Circulating Plasmablasts from Chronically Human Immunodeficiency Virus-Infected Individuals Predominantly Produce Polyreactive/Autoreactive Antibodies
title_short Circulating Plasmablasts from Chronically Human Immunodeficiency Virus-Infected Individuals Predominantly Produce Polyreactive/Autoreactive Antibodies
title_sort circulating plasmablasts from chronically human immunodeficiency virus infected individuals predominantly produce polyreactive autoreactive antibodies
topic human immunodeficiency virus
B cell
plasmablast
polyreactive antibody
autoreactive antibody
Ig heavy
url http://journal.frontiersin.org/article/10.3389/fimmu.2017.01691/full
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