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

David Kuhrt, Seth A. Faith, Amanda Leone, Mukta Rohankedkar, Donald L. Sodora, Louis J. Picker, Kelly Stefano Cole

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2466-2476
Number of pages11
JournalJournal of virology
Volume84
Issue number5
DOIs
StatePublished - Mar 2010

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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