Loss of HIV-specific memory B-cells as a potential mechanism for the dysfunction of the humoral immune response against HIV

Virology. 2010 Feb 5;397(1):7-13. doi: 10.1016/j.virol.2009.11.003. Epub 2009 Dec 4.

Abstract

A central, yet unresolved issue in the pathogenesis of HIV disease is the mechanism of antibody perturbation. In this study, HIV-specific memory B-cells were quantified in groups of infected subjects and compared with memory responses to other antigens and antibody titers. HIV-specific memory B-cell responses were vigorous in individuals with CD4(+) T-cell counts >350/microl and weak or undetectable in subjects with CD4(+) T-cell numbers <200/microl. Memory B-cell loss was permanent, because antiretroviral therapy failed to restore HIV-specific memory responses while influenza- and tetanus toxoid-specific memory B-cells remained unaffected or recovered. Antibody titers to Gag strongly correlated with memory B-cell frequencies. In contrast, Env-specific antibodies were maintained in advanced disease despite low or undetectable levels of memory B-cells. These results provide a potential mechanism by which destruction of HIV-specific CD4(+) T-cells affects the humoral immune response against HIV and compromises the ability to maintain an effective antibody response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Retroviral Agents / therapeutic use
  • Antibodies, Bacterial / blood
  • Antibodies, Viral / blood
  • B-Lymphocytes / immunology*
  • CD4 Lymphocyte Count
  • HIV / immunology*
  • HIV Antibodies / blood
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • Humans
  • Immunologic Memory*
  • Influenza, Human / immunology
  • Tetanus Toxoid / immunology
  • env Gene Products, Human Immunodeficiency Virus / immunology
  • gag Gene Products, Human Immunodeficiency Virus / immunology

Substances

  • Anti-Retroviral Agents
  • Antibodies, Bacterial
  • Antibodies, Viral
  • HIV Antibodies
  • Tetanus Toxoid
  • env Gene Products, Human Immunodeficiency Virus
  • gag Gene Products, Human Immunodeficiency Virus