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

S Moir, J Ho, A Malaspina, W Wang… - The Journal of …, 2008 - rupress.org
S Moir, J Ho, A Malaspina, W Wang, AC DiPoto, MA O'Shea, G Roby, S Kottilil, J Arthos…
The Journal of experimental medicine, 2008rupress.org
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 …
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.
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