HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TAT PROTEIN ACTIVATES B-LYMPHOCYTES

HIV-1 infection causes B cell hyperactivation. Tat protein, a potent v irus-encoded transactivator, has the potential to activate B cells bas ed on its pleiotropic biological properties: (1) Tat regulates cellula r gene expression; (2) Tat modulates growth of various cell types; and (3) Tat is released from infected T cells and acts on bystander uninf ected. cells in a paracrine fashion. To test a possible activating eff ect of Tat on B cells, we examined the effect of purified Tat on the e xpression of Fas, an activation marker, in B cells in primary culture. Flow cytometric analysis demonstrated that treatment of peripheral bl ood mononuclear cells with Tat, at concentrations in the range of extr acellular Tat as determined in vivo, up regulated Fas expression in B cells. Reverse transcriptase-PCR further demonstrated that Tat induced Fas expression in B cells at the mRNA level. These results indicate t hat exogenous Tat alone can activate B cells, suggesting that Tat may contribute to B cell hyperactivation during the early stage ore HIV-1 infection and activation-induced B cell death mediated by Fas during t he late stage of HIV-1 infection. (C) 1997 Academic Press.