Progressive B Cell Apoptosis and Expression of Fas Ligand during Human Immunodeficiency Virus Type 1 Infection

Abstract

HIV-1 infection causes functional defects in T cells. It also leads to a progressive reduction in numbers of such cells and both CD4⁺ and CD8⁺ cells have been reported to undergo apoptosis in culture. A corresponding reduction in B cells has not been described, but these cells are also functionally altered, with reports of polyclonal activation and hyporesponsiveness to antigenic and mitogenic stimuli. Here we investigated B cells from HIV-1-seropositive individuals and found that these cells, which are not the target for virus infection, died of apoptosis on culturing. We could also confirm previous findings that CD4⁺ cells from HIV-1-infected individuals undergo apoptosis in culture. Apoptosis of both B cells and CD4⁺ cells correlated inversely with CD4 cell counts. B cells from HIV-1-infected individuals were found to express Fas ligand, and the expression of this protein correlated with the levels of apoptosis in the same cells. Non-B cells, on the other hand, expressed increased levels of Fas but low levels of Fas ligand. These results are in line with suggestions that the Fas/Fas ligand pathway may trigger the increased levels of apoptosis observed in cells from HIV-1-infected individuals.