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/mu l and weak or undetectable in Subjects with CD4(+) T-cell numbers <200/mu l. 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 OF 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. (C) 2009 Elsevier Inc. All rights reserved.