Inhibition of Fas-mediated apoptosis by antigen: Implications for lymphomagenesis

Elaine J. Schatner, Steven M. Friedman, Paolo Casali

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Apoptotic deletion of expanded B cell populations is essential in avoidance of autoimmune disease and immune regulation of some B cell malignancies. The role of CD4+ T cells in B cell apoptosis is evident from the high incidence of B cell tumors and autoimmunity in patients with T cell diseases such as the acquired immune deficiency syndrome (AIDS). We have previously demonstrated that in Epstein-Barr Virus (EBV) negative Burkitt's lymphoma (BL), a tumor derived from proliferating centroblasts of the germinal center, the malignant lymphocytes can be induced to express Fas (CD95) by ligation of CD40 at the B cell surface. Upon CD40 engagement, BL cells are sensitized to T-cell derived death signals provided by Fas ligand (FasL, CD95L). HBL-3 is a cell line derived from an AIDS-related BL in which the tumor IgM binds the human erythrocyte "i" antigen. To determine whether Fas-mediated apoptosis of BL cells is reduced in the context of antigen to which tumor IgM binds, we stimulated HBL-3 cells with CD40 ligand (CD40L, CD154) in the presence of human erythrocytes expressing the "i" antigen, and measured Fas-mediated apoptosis upon exposure to an agonistic anti-Fas antibody. We observed that HBL-3 cells were sensitized to Fas-mediated death by exposure to CD40L. When i+ RBCs were present, Fas-mediated apoptosis in HBL-3 cells was reduced by greater than 30%. In contrast, there was no reduction in Fas-mediated apoptosis in the presence of i- (I+) RBCs. These findings demonstrated that Fas-mediated deletion of BL cells is inhibited upon surface IgM engagement by antigen for which the malignant clone has affinity.

Original languageEnglish (US)
Pages (from-to)283-289
Number of pages7
JournalAutoimmunity
Volume35
Issue number4
DOIs
StatePublished - 2002

Keywords

  • Apoptosis
  • B lymphocytes
  • Burkitt's lymphoma
  • Fas (CD95)
  • Human immunodeficiency virus (HIV)
  • Immunoglobulin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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