Identification of Immunosuppressant-Induced Apoptosis in a Murine B-Cell Line and its Prevention by bcl-x but not bcl-2

Cyclosporin A, FK-506, and rapamycin are immunosuppressants often used as pharmacological probes to study lymphocyte activation and physiological cell death (PCD). Because cyclosporin A and FK-506 are known to prevent PCD in T-cell hybridomas and thymocytes, we used these reagents, as well as rapamy...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1994-07, Vol.91 (15), p.7350-7354
Main Authors: Gottschalk, Alexander R., Boise, Lawrence H., Thompson, Craig B., Quintans, Jose
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - drug effects
Apoptosis - genetics
B lymphocytes
B-Lymphocytes - cytology
B-Lymphocytes - drug effects
B-Lymphocytes - immunology
bcl-X Protein
Cell cycle
Cell growth
Cell Line
Cell lines
Cyclosporine - pharmacology
Cyclosporins
Fungi
Humans
Immunity (Disease)
Immunosuppressants
Immunosuppressive Agents - pharmacology
Lymphocytes
Medical research
Mice
Proteins
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - physiology
Proto-Oncogene Proteins c-bcl-2
T lymphocytes
Tacrolimus - pharmacology
Vehicles
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Summary:Cyclosporin A, FK-506, and rapamycin are immunosuppressants often used as pharmacological probes to study lymphocyte activation and physiological cell death (PCD). Because cyclosporin A and FK-506 are known to prevent PCD in T-cell hybridomas and thymocytes, we used these reagents, as well as rapamycin, to determine whether they alter the pathway leading to apoptosis in murine WEHI-231 cells following surface IgM cross-linking. We observed that the immunosuppressants themselves induced PCD in WEHI-231 cells, but only in sublines susceptible to anti-IgM-mediated apoptosis. PCD was preceded by growth arrest and characterized by the DNA fragmentation pattern typical of apoptosis. In B-cell lines resistant to anti-immunoglobulin- and immunosuppressant-induced PCD, cyclosporin A, FK-506, and rapamycin caused growth arrest. PCD was also induced by inhibitors of protein synthesis in WEHI-231 cells but not in the mature B-cell line BAL-17. Immunosuppressant-induced and protein synthesis inhibitor-induced PCD, but not growth arrest, could be prevented by the overexpression of bcl-xL, while transfection with bcl-2 did not affect PCD or cell cycle arrest. These results suggest that bcl-2 and bcl-xLmay control partially independent systems to inhibit PCD in lymphoid cells and that PCD in B and T cells may be differentially regulated.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.91.15.7350