Regulation of fas-mediated apoptosis of birkht's lymphoma b cells
Gene Expression Regulation, Leukemic
Gene Expression Regulation, Viral
Herpesvirus 4, Human
Herpesvirus 8, Human
Fas ligtnd is selectively expressed by CD4+ T cells and represents the major mechanism of CD4+ T cell-mediated cytotoxicity. Activated CD4+ T cells also express CD40 Ligand, which is a crucial regulator of T cell-dependent B cell activation. We have reported mat CD4+ T cells can modulate die growth of Burkitl's lymphoma (BL) B cells by tigating CD40 at the B cell surface, which results in increased surface expression of Fas on B cells and confers susceptibility to Fas-mediated death signals. We have now analyzed cells from a panel of BL cell lines and fresh BL clinical samples for Fas upregulation and susceptibility to apoptosis after CD40 ligation. Using flow cytometry and immunofluorescence, we demonstrated that at) the BL cells constitutively expressed low levels of Fas and responded to CD40 ligation by upregulating Fas. Cell viability, proliferation, and DNA analyses, with and without exposure to an agonistic anti-Fas monoclonal antibody, indicated that once Fas was upregulated, susceptibility to Fas-mediated apoptosis varied considerably. In this system, cells that expressed Epstein Barr Virus gene products were relatively resistant to Fas-mediated apoptosis. Cells that were exposed to antiIgM, which crosslinks the surface antigen receptor, were also protected, in a manner that depended on the concentration of the IgM crosslraking agentThèse mechanisms of resistance to Fas-mediated cytolysis may have important implications concerning the etiology and therapy of BL.