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

Autoimmunity. 2002 Jul;35(4):283-9. doi: 10.1080/0891693021000002072.


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 the tumor IgM binds, we stimulated HBL-3 cells with CD40 ligand (CD40L, CD154) in the presence and absence 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 demonstrate that Fas-mediated deletion of BL cells is inhibited upon surface IgM engagement by antigen for which the malignant clone has affinity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS-Related Opportunistic Infections / immunology
  • Antigens / immunology*
  • Apoptosis* / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Burkitt Lymphoma / immunology
  • Burkitt Lymphoma / physiopathology*
  • CD40 Antigens / immunology
  • CD40 Ligand / immunology
  • Cell Line
  • Erythrocytes / immunology*
  • Humans
  • Lymphocyte Activation
  • Tumor Cells, Cultured
  • fas Receptor / immunology*
  • fas Receptor / metabolism


  • Antigens
  • CD40 Antigens
  • fas Receptor
  • CD40 Ligand