Regulation of memory B-cell survival by the BH3-only protein Puma

Cyril Clybouw, Silke Fischer, Marie Thérèse Auffredou, Patricia Hugues, Catherine Alexia, Philippe Bouillet, Martine Raphael, Gérald Leca, Andreas Strasser, David M. Tarlinton, Aimé Vazquez

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26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4120-4128
Number of pages9
JournalBlood
Volume118
Issue number15
DOIs
Publication statusPublished - 13 Oct 2011
Externally publishedYes

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