Different Pattern of Immunoglobulin Gene Usage by HIV-1 Compared to Non-HIV-1 Antibodies Derived from the Same Infected Subject

• Type of Material: Article
• Authors: Liuzhe Li, New York University; Xiao-Hong Wang, Veterans Affairs New York Harbor Healthcare System; Sagarika Banerjee, New York University; Barbara Volsky, New York University; Constance Williams, New York University; Diana Virland, Veterans Affairs New York Harbor Healthcare System; Arthur Nadas, New York University; Michael S. Seaman, Harvard University; Xuemin Chen, Emory University; Paul Spearman, Emory University; Susan Zolla-Pazner, New York University; Miroslaw K. Gorny, New York University
• Language: English
• Date: 2012-06-25
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Li et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0039534
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 7
• Issue: 6
• Start Page: e39534
• End Page: e39534
• Grant/Funding Information: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; The study was supported by NIH grants AI091543 and AI077451 to MKG, and by HL59725 and research funds from the Department of Veterans Affairs to SZP.
• Keywords: FAMILY EXPRESSION; HUMAN MONOCLONAL-ANTIBODIES; Science & Technology - Other Topics; V3 DOMAIN; PARTICLES BEARING; Science & Technology; MEMORY B-CELLS; PBL-SCID MICE; HUMAN-IMMUNODEFICIENCY-VIRUS; Multidisciplinary Sciences; MULTIDISCIPLINARY SCIENCES; ENVELOPE PROTEINS; NEUTRALIZING ANTIBODIES; PASSIVE-IMMUNIZATION
• Research Categories: Health Sciences, Immunology; Health Sciences, Pathology

Abstract

A biased usage of immunoglobulin (Ig) genes is observed in human anti-HIV-1 monoclonal antibodies (mAbs) resulting probably from compensation to reduced usage of the VH3 family genes, while the other alternative suggests that this bias usage is due to antigen requirements. If the antigen structure is responsible for the preferential usage of particular Ig genes, it may have certain implications for HIV vaccine development by the targeting of particular Ig gene-encoded B cell receptors to induce neutralizing anti-HIV-1 antibodies. To address this issue, we have produced HIV-1 specific and non-HIV-1 mAbs from an infected individual and analyzed the Ig gene usage. Green-fluorescence labeled virus-like particles (VLP) expressing HIV-1 envelope (Env) proteins of JRFL and BaL and control VLPs (without Env) were used to select single B cells for the production of 68 recombinant mAbs. Ten of these mAbs were HIV-1 Env specific with neutralizing activity against V3 and the CD4 binding site, as well as non-neutralizing mAbs to gp41. The remaining 58 mAbs were non-HIV-1 Env mAbs with undefined specificities. Analysis revealed that biased usage of Ig genes was restricted only to anti-HIV-1 but not to non-HIV-1 mAbs. The VH1 family genes were dominantly used, followed by VH3, VH4, and VH5 among anti-HIV-1 mAbs, while non-HIV-1 specific mAbs preferentially used VH3 family genes, followed by VH4, VH1 and VH5 families in a pattern identical to Abs derived from healthy individuals. This observation suggests that the biased usage of Ig genes by anti-HIV-1 mAbs is driven by structural requirements of the virus antigens rather than by compensation to any depletion of VH3 B cells due to autoreactive mechanisms, according to the gp120 superantigen hypothesis.