CD4+ T-cell induction of Fas-mediated apoptosis in Burkitt's lymphoma B cells.
Cytotoxic function of CD4+ Th1 cells is mediated by Fas (CD95, APO-1) and its ligand (Fas ligand). Recent studies using nontransformed B cells and the Ramos Burkitt's lymphoma (BL) B-cell line cells show that CD40 ligation at the B-cell surface by activated, CD40 ligand (CD40L)-bearing, CD4+ T cells upregulates Fas expression on B cells and primes B cells for Fas-mediated death signals. In this work, we examine whether this CD4+ T-cell-dependent molecular pathway for Fas upregulation and B-cell apoptosis reflects a peculiarity of the Ramos B-cell line or is applicable to other Burkitt's tumors as well. In 5 of the 6 Epstein-Barr virus-negative BL cell lines examined, the cells constitutively express undetectable or low levels of Fas and are resistant to Fas-mediated signals induced by monoclonal anti-Fas antibody. All 6 of the BL cell line B cells upregulate Fas in response to CD40 ligation, and in 4 of the cases they become sensitive to Fas-mediated death signals. In one BL cell line, the cells are constitutively sensitive to Fas-mediated cytolysis and are unaffected by CD40 signals. Next, we applied these immunologic manipulations to cells from a refractory clinical sample and observed that the tumor cells could be induced to express Fas and undergo apoptosis in our system. These results establish CD4+ T cells and the Fas-Fas ligand system as important immune regulators of Burkitt's lymphoma B cells and indicate that the susceptibility of tumor cells to Fas-mediated death signals can be modulated by specific activation events at the cell surface.
Schattner
E J
EJ
Department of Medicine, New York Hospital-Cornell Medical Center 10021, USA.
Mascarenhas
J
J
Bishop
J
J
Yoo
D H
DH
Chadburn
A
A
Crow
M K
MK
Friedman
S M
SM
D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology; D002051:Burkitt Lymphoma / Q000276:immunology / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D019014:fas Receptor; D023201:CD40 Ligand