title: Regulation of memory B-cell survival by the BH3-only protein Puma.
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.
authors.affiliation: Inserm Unité Mixte de Recherche (UMR)-S 1014, Villejuif, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Clybouw
authors.forename: Silke
authors.initials: S
authors.lastname: Fischer
authors.forename: Marie Thérèse
authors.initials: MT
authors.lastname: Auffredou
authors.forename: Patricia
authors.initials: P
authors.lastname: Hugues
authors.forename: Catherine
authors.initials: C
authors.lastname: Alexia
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouillet
authors.forename: Martine
authors.initials: M
authors.lastname: Raphael
authors.forename: Gérald
authors.initials: G
authors.lastname: Leca
authors.forename: Andreas
authors.initials: A
authors.lastname: Strasser
authors.forename: David M
authors.initials: DM
authors.lastname: Tarlinton
authors.forename: Aimé
authors.initials: A
authors.lastname: Vazquez
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D008934:Mitogens / Q000494:pharmacology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; C579094:Mcl1 protein, mouse; D008934:Mitogens; D064549:Myeloid Cell Leukemia Sequence 1 Protein; C488588:PUMA protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D025521:Tumor Suppressor Proteins