HIV-1 induces phenotypic and functional perturbations of B cells in chronically infected individuals

HIV-1 诱导慢性感染者 B 细胞表型和功能紊乱

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作者:S Moir, A Malaspina, K M Ogwaro, E T Donoghue, C W Hallahan, L A Ehler, S Liu, J Adelsberger, R Lapointe, P Hwu, M Baseler, J M Orenstein, T W Chun, J A Mican, A S Fauci

Abstract

A number of perturbations of B cells has been described in the setting of HIV infection; however, most remain poorly understood. To directly address the effect of HIV replication on B cell function, we investigated the capacity of B cells isolated from HIV-infected patients to respond to a variety of stimuli before and after reduction of viremia by effective antiretroviral therapy. B cells taken from patients with high levels of plasma viremia were defective in their proliferative responses to various stimuli. Viremia was also associated with the appearance of a subpopulation of B cells that expressed reduced levels of CD21. After fractionation into CD21(high)- and CD21(low)-expressing B cells, the CD21(low) fraction showed dramatically reduced proliferation in response to B cell stimuli and enhanced secretion of immunoglobulins when compared with the CD21(high) fraction. Electron microscopic analysis of each fraction revealed cells with plasmacytoid features in the CD21(low) B cell population but not in the CD21(high) fraction. These results indicate that HIV viremia induces the appearance of a subset of B cells whose function is impaired and which may be responsible for the hypergammaglobulinemia associated with HIV disease.

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