The avian chB6 alloantigen induces apoptosis in DT40 B cells

• Published in: Cellular immunology Vol. 226; no. 2; pp. 95 - 104
• Main Authors: Funk, Phillip E, Pifer, Jeannette, Kharas, Michael, Crisafi, Gina, Johnson, Amy
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.12.2003
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - immunology; B-lymphocytes; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; B-Lymphocytes - ultrastructure; bcl-X Protein; Birds - immunology; Blotting, Western; Caspases - drug effects; Caspases - immunology; Cell surface molecules; Enzyme Inhibitors - pharmacology; In Situ Nick-End Labeling; Isoantigens - immunology; Membrane Potentials - physiology; Mitochondria - pathology; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - immunology; Signal Transduction - immunology; Transfection; Cell surface molecules; B-lymphocytes; Apoptosis
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2003.11.009

In avian species, B-lymphocytes develop in the bursa of Fabricius. Cells developing in the bursa are subject to signals regulating their survival, with the majority of cells dying by apoptosis within the bursa. However, the molecules delivering the signals influencing this life and death decision remain enigmatic. We have previously shown that antibodies against the chB6 alloantigen present on avian B-lymphocytes can induce a rapid form of cell death. Here we extend this finding by showing that anti-chB6 antibodies induce true apoptosis in DT40 cells without visible membrane damage. This apoptosis results in DNA degradation and morphologic changes characteristic of apoptosis. Furthermore, this apoptosis is coincident with a loss of mitochondrial membrane potential and is inhibited by either overexpression of bcl-x L or the presence of inhibitors of caspase 8, 9, or 3 activity. Collectively these data argue that chB6 may function as a novel death receptor on avian B-lymphocytes and support the use of DT40 as an amenable model to study the signaling involved in chB6-induced apoptosis.