CD4+ T-cell induction of Fas-mediated apoptosis in Burkitt's lymphoma B cells.

TitleCD4+ T-cell induction of Fas-mediated apoptosis in Burkitt's lymphoma B cells.
Publication TypeJournal Article
Year of Publication1996
AuthorsSchattner EJ, Mascarenhas J, Bishop J, Yoo DH, Chadburn A, Crow MK, Friedman SM
Date Published1996 Aug 15
KeywordsApoptosis, B-Lymphocytes, Burkitt Lymphoma, CD4-Positive T-Lymphocytes, CD40 Antigens, CD40 Ligand, Cell Division, Cytotoxicity, Immunologic, fas Receptor, Humans, Membrane Glycoproteins, T-Lymphocyte Subsets, Tumor Cells, Cultured

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.

Alternate JournalBlood
PubMed ID8695856
Grant ListP50 AR42588-02 / AR / NIAMS NIH HHS / United States
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