HIV-1 induces phenotypic and functional perturbations of B cells in chronically infected individuals |
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| Authors: | Moir S Malaspina A Ogwaro K M Donoghue E T Hallahan C W Ehler L A Liu S Adelsberger J Lapointe R Hwu P Baseler M Orenstein J M Chun T W Mican J A Fauci A S |
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| Affiliation: | Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, and Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. smoir@niaid.nih.gov |
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| 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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