Evidence of Early B-Cell Dysregulation in Simian Immunodeficiency Virus Infection: Rapid Depletion of Naïve and Memory B-Cell Subsets with Delayed Reconstitution of the Naïve B-Cell Population

Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Journal of Virology (Impact Factor: 4.65). 03/2010; 84(5):2466-76. DOI: 10.1128/JVI.01966-09
Source: PubMed

ABSTRACT Despite eliciting a robust antibody response in humans, several studies in human immunodeficiency virus (HIV)-infected patients have demonstrated the presence of B-cell deficiencies during the chronic stage of infection. While several explanations for the HIV-induced B-cell deficit have been proposed, a clear mechanistic understanding of this loss of B-cell functionality is not known. This study utilizes simian immunodeficiency virus (SIV) infection of rhesus macaques to assess B-cell population dynamics beginning at the acute phase and continuing through the chronic phase of infection. Flow cytometric assessment demonstrated a significant early depletion of both naïve and memory B-cell subsets in the peripheral blood, with differential kinetics for recovery of these populations. Furthermore, the altered numbers of naïve and memory B-cell subsets in these animals corresponded with increased B-cell activation and altered proliferation profiles during the acute phase of infection. Finally, all animals produced high titers of antibody, demonstrating that the measurement of virus-specific antibody responses was not an accurate reflection of alterations in the B-cell compartment. These data indicate that dynamic B-cell population changes in SIV-infected macaques arise very early after infection at the precise time when an effective adaptive immune response is needed.

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