Regulation of memory B-cell survival by the BH3-only protein Puma
Regulation of memory B-cell survival by the BH3-only protein Puma
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DOI：
10.1182/blood-2011-04-347096
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发表时间：
2011-10-13
期刊：
影响因子：
20.3
通讯作者：
Vazquez, Aime
中科院分区：
文献类型：
--
作者：
Clybouw, Cyril;Fischer, Silke;Vazquez, Aime
细胞凋亡对于免疫系统稳态至关重要，包括长寿命抗体形成细胞和记忆细胞的选择和存活。Bcl-2家族的促凋亡蛋白和促存活蛋白之间的相互作用对于该过程至关重要。在这份报告中，我们表明，表达的促凋亡BH 3-只有Bcl-2家族成员彪马选择性上调体外激活抗原或有丝分裂原的人类和小鼠B细胞。Puma的表达与伯基特淋巴瘤的生发中心内的促生存Bcl-2家族成员Mcl-1在体内一致，并且其表达与伯基特淋巴瘤的生发中心样表型相关。在Puma缺陷小鼠中进行的实验表明，Puma对于体外促分裂原激活的B细胞的凋亡和记忆B细胞存活的控制是必需的。总之，使用人类和小鼠模型，我们的数据表明，彪马在T细胞依赖性B细胞免疫应答中起着重要作用。这些数据表明，Puma是记忆B淋巴细胞存活的主要调节因子，因此是控制免疫应答的关键分子。（血。2011; 118（15）：4120-4128）
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)