Journal article
The BH3-Only Proteins Bim and Puma Cooperate to Impose Deletional Tolerance of Organ-Specific Antigens
DHD Gray, F Kupresanin, SP Berzins, MJ Herold, LA O'Reilly, P Bouillet, A Strasser
Immunity | Published : 2012
Abstract
Although the proapoptotic BH3-only protein, Bim, is required for deletion of autoreactive thymocytes, Bim-deficient mice do not succumb to extensive organ-specific autoimmune disease. To determine whether other BH3-only proteins safeguard tolerance in the absence of Bim, we screened mice lacking Bim as well as other BH3-only proteins. Most strains showed no additional defects; however, mice deficient for both Puma and Bim spontaneously developed autoimmunity in multiple organs, and their T cells could transfer organ-specific autoimmunity. Puma- and Bim-double-deficient mice had a striking accumulation of mature, single-positive thymocytes, suggesting an additional defect in thymic deletion w..
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Awarded by National Institutes of Health
Funding Acknowledgements
We gratefully acknowledge C. Thompson (Memorial Sloan-Kettering Cancer Center, New York) for the kind gift of Bak<SUP>-/-</SUP> mice, N. Danial (Dana-Farber Cancer Institute, Boston) for Bad<SUP>-/-</SUP> mice, and T. Jacks (Massachusetts Institute of Technology, Cambridge, MA, USA) for Trp53<SUP>-/-</SUP> mice; K. Mason and D. Huang for the provision of Bax<SUP>-/-</SUP>Bak<SUP>-/-</SUP> mouse fetal livers; G. Dewson for the provision of antibodies; G. Siciliano, K. Vella, K. Trueman, and G.-F. Dabrowski for animal care; and B. Holbert, C. Young, A. Policheni, and the WEHI Cytometry and Histology Facilities for technical assistance. This work was supported by the Australian National Health and Medical Research Council (NHMRC project grants 637332 and 1009145, Australia Fellowship to A.S., and Career Development Fellowship (637353) to D.H.D.G), the Juvenile Diabetes Foundation, the Leukemia and Lymphoma Society (New York; Specialized Center of Research grant 7413), and the National Cancer Institute (National Institutes of Health; CA 43540). This work was made possible through Victorian State Government Operational Infrastructure Support and the Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme.