Inhibition of Fas-mediated Apoptosis by Antigen: Implications for Lymphomagenesis

• Published in: Autoimmunity (Chur, Switzerland) Switzerland), 2002, Vol.35 (4), p.283-289
• Main Authors: Schattner, Elaine J., Friedman, Steven M., Casali, Paolo
• Format: Article
• Language: English
• Subjects: AIDS-Related Opportunistic Infections - immunology; Antigens - immunology; Apoptosis; Apoptosis - immunology; B Lymphocytes; B-Lymphocytes - immunology; B-Lymphocytes - pathology; Biological and medical sciences; Burkitt Lymphoma - immunology; Burkitt Lymphoma - physiopathology; Burkitt's Lymphoma; CD40 Antigens - immunology; CD40 Ligand - immunology; Cell Line; Erythrocytes - immunology; Fas (CD95); fas Receptor - immunology; fas Receptor - metabolism; Hematologic and hematopoietic diseases; Human Immunodeficiency Virus (HIV); Human viral diseases; Humans; Immunoglobulin; Infectious diseases; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocyte Activation; Medical sciences; Tumor Cells, Cultured; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0891-6934; 1607-842X
• 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 &#109 (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.