Human immunodeficiency virus type 1 TAT protein activates B lymphocytes.
HIV-1 infection causes B cell hyperactivation. Tat protein, a potent virus-encoded transactivator, has the potential to activate B cells based on its pleiotropic biological properties: (1) Tat regulates cellular gene expression; (2) Tat modulates growth of various cell types; and (3) Tat is released from infected T cells and acts on bystander uninfected cells in a paracrine fashion. To test a possible activating effect of Tat on B cells, we examined the effect of purified Tat on the expression of Fas, an activation marker, in B cells in primary culture. Flow cytometric analysis demonstrated that treatment of peripheral blood mononuclear cells with Tat, at concentrations in the range of extracellular 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 that exogenous Tat alone can activate B cells, suggesting that Tat may contribute to B cell hyperactivation during the early stage of HIV-1 infection and activation-induced B cell death mediated by Fas during the late stage of HIV-1 infection.
Huang
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Department of Biological Chemistry and Molecular Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts, 02115, USA. meihua@mbcrr.harvard.edu
Li
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Pardee
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D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002469:Cell Separation; D005434:Flow Cytometry; D015696:Gene Products, tat / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology*; D019014:fas Receptor / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D019014:fas Receptor; D054322:tat Gene Products, Human Immunodeficiency Virus