Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals

721Citations
Citations of this article
396Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Human immunodeficiency virus (HIV) disease leads to impaired B cell and antibody responses through mechanisms that remain poorly defined. A unique memory B cell subpopulation (CD20hi /CD27lo/CD21 lo) in human tonsillar tissues was recently defined by the expression of the inhibitory receptor Fc-receptor-like-4 (FCRL4). In this study, we describe a similar B cell subpopulation in the blood of HIV-viremic individuals. FCRL4 expression was increased on B cells of HIV-viremic compared with HIV-aviremic and HIV-negative individuals. It was enriched on B cells with a tissuelike memory phenotype (CD20hi /CD27- /CD21 lo) when compared with B cells with a classical memory (CD27 +) or naive (CD27-/CD21hi) B cell phenotype. Tissuelike memory B cells expressed patterns of homing and inhibitory receptors similar to those described for antigen-specific T cell exhaustion. The tissuelike memory B cells proliferated poorly in response to B cell stimuli, which is consistent with high-level expression of multiple inhibitory receptors. Immunoglobulin diversities and replication histories were lower in tissuelike, compared with classical, memory B cells, which is consistent with premature exhaustion. Strikingly, HIV-specific responses were enriched in these exhausted tissuelike memory B cells, whereas total immunoglobulin and influenza-specific responses were enriched in classical memory B cells. These data suggest that HIV-associated premature exhaustion of B cells may contribute to poor antibody responses against HIV in infected individuals.

Cite

CITATION STYLE

APA

Moir, S., Ho, J., Malaspina, A., Wang, W., DiPoto, A. C., O’Shea, M. A., … Fauci, A. S. (2008). Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals. Journal of Experimental Medicine, 205(8), 1797–1805. https://doi.org/10.1084/jem.20072683

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free