The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20072683
The Journal of Experimental Medicine, Vol. 205, No. 8, 1797-1805
The Rockefeller University Press, 0022-1007 $30.00
© Moir et al.
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BRIEF DEFINITIVE REPORT

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

Susan Moir1, Jason Ho1, Angela Malaspina1, Wei Wang1, Angela C. DiPoto1, Marie A. O'Shea1, Gregg Roby1, Shyam Kottilil1, James Arthos1, Michael A. Proschan2, Tae-Wook Chun1, and Anthony S. Fauci1

1 Laboratory of Immunoregulation and 2 Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892

CORRESPONDENCE Susan Moir: smoir{at}niaid.nih.gov

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/CD21lo) 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–/CD21lo) 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.

S. Moir and J. Ho contributed equally to this paper.


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