B-Lymphocyte Dysfunction in Chronic HIV-1 Infection Does Not Prevent Cross-Clade Neutralization Breadth

• Type of Material: Article
• Authors: Saikat Boliar, Emory University; Megan K. Murphy, Emory University; T. Cameron Tran, Emory University; Diane G. Carnathan, Emory University; Wendy S. Armstrong, Emory University; Guido Silvestri, Emory University; Cynthia Derdeyn, Emory University
• Language: English
• Date: 2012-08
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2012, American Society for Microbiology. All Rights Reserved.
• Final Published Version (URL): http://jvi.asm.org/content/86/15/8031
• Title of Journal or Parent Work: Journal of Virology
• Volume: 86
• Issue: 15
• Start Page: 8031
• End Page: 8040
• Grant/Funding Information: This work was supported by the National Institutes of Health through grants R01-AI58706 to C.A.D. and P30-AI050409 to the Emory University Center for AIDS Research, supporting the Clinical Research, Immunology, and Virology cores.
• Research Categories: Biology, Virology; Health Sciences, Pathology

Abstract

Aberrant expression of regulatory receptors programmed death-1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) is linked with dysregulation and exhaustion of T lymphocytes during chronic human immunodeficiency virus type 1 (HIV-1) infection; however, less is known about whether a similar process impacts B-lymphocyte function during HIV-1 infection. We reasoned that disruption of the peripheral B cell compartment might be associated with decreased neutralizing antibody activity. Expression of markers that indicate dysregulation (BTLA and PD-1), immune activation (CD95), and proliferation (Ki-67) was evaluated in B cells from HIV-1-infected viremic and aviremic subjects and healthy subjects, in conjunction with immunoglobulin production and CD4 T cell count. Viral load and cross-clade neutralizing activity in plasma from viremic subjects were also assessed. Dysregulation of B lymphocytes was indicated by a marked disruption of peripheral B cell subsets, increased levels of PD-1 expression, and decreased levels of BTLA expression in viremic subjects compared to aviremic subjects and healthy controls. PD-1 and BTLA were correlated in a divergent fashion with immune activation, CD4 T cell count, and the total plasma IgG level, a functional correlate of B cell dysfunction. Within viremic subjects, the total IgG level correlated directly with cross-clade neutralizing activity in plasma. The findings demonstrate that even in chronically infected subjects in which B lymphocytes display multiple indications of dysfunction, antibodies that mediate cross-clade neutralization breadth continue to circulate in plasma.