Loss of HIV-specific memory B-cells as a potential mechanism for the dysfunction of the humoral immune response against HIV.
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.
Bussmann
Bianca M
BM
Institute of Virology, Max Bürger Research Center, Universität Leipzig, 04103 Leipzig, Germany.
Reiche
Sven
S
Bieniek
Bernhard
B
Krznaric
Ivanka
I
Ackermann
Frank
F
Jassoy
Christian
C
D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D000907:Antibodies, Bacterial / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D006678:HIV / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007251:Influenza, Human / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
D044966:Anti-Retroviral Agents; D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D015483:HIV Antibodies; D013745:Tetanus Toxoid; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus