Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / physiology*
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Apoptosis Regulatory Proteins / biosynthesis
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / immunology*
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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Cell Line, Tumor
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology
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Humans
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Immunologic Memory / drug effects
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Immunologic Memory / physiology*
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / physiology
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Mice
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Mice, Mutant Strains
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Mitogens / pharmacology
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Myeloid Cell Leukemia Sequence 1 Protein
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / immunology*
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / immunology
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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Tumor Suppressor Proteins / biosynthesis
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Tumor Suppressor Proteins / genetics
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Tumor Suppressor Proteins / immunology*
Substances
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Apoptosis Regulatory Proteins
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BBC3 protein, human
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Mcl1 protein, mouse
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Mitogens
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Myeloid Cell Leukemia Sequence 1 Protein
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PUMA protein, mouse
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Tumor Suppressor Proteins