Journal
BLOOD
Volume 118, Issue 15, Pages 4120-4128Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-04-347096
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Funding
- Inserm
- Ligue Nationale contre le Cancer (Equipe labellisee)
- Agence Nationale de la Recherche (ANR)
- Canceropole IdF
- National Health and Medical Research Council (Australia) [257502, 356202]
- Leukemia & Lymphoma Society (New York) [7015]
- National Cancer Institute (National Institutes of Health) [CA80188, CA43540]
- Fondation pour la Recherche Medicale
- Association pour le Recherche sur le Cancer (ARC)
- Deutsche Forschungsgemeinschaft
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Apoptosis is crucial for immune system homeostasis, including selection and survival of long-lived antibody-forming cells and memory cells. The interactions between proapoptotic and pro-survival proteins of the Bcl-2 family are critical for this process. In this report, we show that expression of the proapoptotic BH3-only Bcl-2 family member Puma was selectively up-regulated on in vitro activation with antigens or mitogens of both human and mouse B cells. Puma expression coincided in vivo, with the prosurvival Bcl-2 family member Mcl-1 within the germinal centers and its expression correlates with the germinal center like phenotype of Burkitt lymphoma. Experiments performed in Puma-deficient mice revealed that Puma is essential for apoptosis of mitogen-activated B cells in vitro and for the control of memory B-cell survival. In conclusion, using both human and murine models, our data show that Puma has a major role in the T cell-dependent B-cell immune response. These data demonstrate that Puma is a major regulator of memory B lymphocyte survival and therefore a key molecule in the control of the immune response. (Blood. 2011; 118(15):4120-4128)
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