Apoptosis and polyclonal B-cell activation during HIV-1 infection

The B-cell abnormalities frequently associated with HIV-1 infection include both extensive hyperactivity and a marked hyporesponsiveness to diverse stimuli. We studied how such abnormalities of the B-cell function were related to disease progression and viral burden in HIV-l-infected individuals. Specificially, the priming of B-cells for apoptosis, the composition of the B-cell population, and spontaneous IgG secretion were investigated. We found that both the B-cells as well as the CD4(+) T-cells from HN-l-infected individuals undergo extensive apoptosis upon in vitro culture. Furthermore, the extent of apoptosis in both these cell types increased in patients with a low CD4 cell count, rapid disease progression and a high viral load. In contrast, spontaneous IgG secretion was evident mainly in infected individuals with a relatively intact immune system as determined by CD4 cell counts. The distribution of naive versus memory B-cells was similar in uninfected and infected individuals. But, a specific loss of CD23(+) B-cells was observed in HIV-l-infected patients. Overall, the substantial hyperactivity of B-lymphocytes driven by the systemic infection may eventually contribute to the progressive deterioration of the B-cell pool in HIV-1-infected patients.