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

J Virol. 2010 Mar;84(5):2466-76. doi: 10.1128/JVI.01966-09. Epub 2009 Dec 23.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Immunity / physiology
  • Animals
  • Antigens, CD20 / immunology
  • B-Lymphocyte Subsets* / immunology
  • B-Lymphocyte Subsets* / virology
  • B-Lymphocytes* / immunology
  • B-Lymphocytes* / virology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • Cell Differentiation / immunology
  • Cell Proliferation
  • Humans
  • Immunoglobulin D / immunology
  • Macaca mulatta / immunology
  • Macaca mulatta / virology
  • Simian Acquired Immunodeficiency Syndrome / immunology*
  • Simian Immunodeficiency Virus / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology
  • Viral Load
  • fas Receptor / immunology

Substances

  • Antigens, CD20
  • Immunoglobulin D
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • fas Receptor