Circulating plasmablasts from chronically human immunodeficiency virus-infected individuals predominantly produce polyreactive/autoreactive antibodies

Hongyan Liao, Yangsheng Yu, Song Li, Yinshi Yue, Chuanmin Tao, Kaihong Su, Zhixin Zhang

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number1691
JournalFrontiers in immunology
Volume8
Issue numberDEC
DOIs
StatePublished - Dec 6 2017

Keywords

  • Autoreactive antibody
  • B cell
  • Human immunodeficiency virus
  • Ig heavy
  • Plasmablast
  • Polyreactive antibody
  • Repertoire
  • VH replacement

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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