BANK negatively regulates Akt activation and subsequent B cell responses
BANK negatively regulates Akt activation and subsequent B cell responses
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DOI：
10.1016/j.immuni.2006.01.002
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发表时间：
2006-03-01
期刊：
影响因子：
32.4
通讯作者：
Kurosaki, T
中科院分区：
文献类型：
--
作者：
Aiba, Y;Yamazaki, T;Kurosaki, T
BANK是一种在B细胞中高表达的适配蛋白。为了研究其生理作用，我们制造了bank缺陷小鼠。对于t依赖性抗原，缺乏bank的小鼠表现出增强的生发中心形成和IgM产生，而在CD40-BANK双敲除小鼠中，这种表型被阻断。体外分析进一步证实了BANK参与CD40信号传导。在缺乏bank的B细胞中，cd40介导的增殖和存活显著增加，Akt激活增强，而在缺乏bank的B细胞中引入显性阴性Akt抑制了cd40介导的增强反应。总之，我们的研究结果表明，BANK可减弱cd40介导的Akt活化，从而防止过度活跃的B细胞反应。
BANK is an adaptor protein that is highly expressed in B cells. To investigate its physiological role, we generated BANK-deficient mice. BANK-deficient mice displayed enhanced germinal center formation and IgM production in response to T-dependent antigens, whereas this phenotype was blocked in CD40-BANK double knockout mice. Involvement of BANK in CD40 signaling was further demonstrated by in vitro analysis. CD40-mediated proliferation and survival were significantly increased in BANK-deficient B cells, with enhanced Akt activation, whereas introduction of dominant-negative Akt into BANK-deficient B cells suppressed the augmented CD40-mediated responses. Together, our findings suggest that BANK attenuates CD40-mediated Akt activation, thereby preventing hyperactive B cell responses.