B-cell responses to B-cell activation factor of the TNF family (BAFF) are impaired in the absence of PI3K delta
B-cell responses to B-cell activation factor of the TNF family (BAFF) are impaired in the absence of PI3K delta
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DOI：
10.1002/eji.200838618
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发表时间：
2008-12-01
影响因子：
5.4
通讯作者：
Turner, Martin
中科院分区：
文献类型：
--
作者：
Henley, Thomas;Kovesdi, Dorottya;Turner, Martin
肿瘤坏死因子家族的B细胞激活因子（BAFF）对B细胞的存活和成熟至关重要。BAFF调节发育中B细胞存活的分子机制正逐渐被更好地理解。近期开始有证据表明PI3K/Akt信号通路在对BAFF的应答中起作用。然而，PI3K家族对BAFF信号传导的重要性以及PI3K功能缺失对BAFF应答的影响仍然未知。因此，我们研究了PI3K催化亚基P110δ缺失的B细胞对BAFF介导的应答。我们发现P110δ的缺失损害了培养的B细胞中BAFF介导的存活，这表明PI3K家族的这一成员在调节B细胞对BAFF应答的存活中具有直接作用。P110δ是B细胞对BAFF应答的生长所必需的，并且对B细胞受体（BCR）交联后BAFF受体的上调至关重要。我们的研究结果揭示了p110δ在调节B细胞对BAFF的应答中具有重要作用。
B-cell activating factor of the TNF family (BAFF) is critical for the survival and maturation of B cells. The molecular mechanisms by which BAFF regulates the survival of developing B cells are becoming better understood. Recent evidence has begun to emerge demonstrating a role for the PI3K/Akt signalling pathway in response to BAFF. However, the importance of the PI3K family for BAFF-signalling and the effects of loss of PI3K function on BAFF responses are still unknown. We therefore investigated the BAFF-mediated responses of B cells deficient for the PI3K catalytic subunit P110 delta. We find that the loss of P110 delta impairs the BAFF-mediated survival of cultured B cells demonstrating a direct role for this member of the PI3K family in regulating the survival of B cells in response to BAFF. P110 delta was required for the growth of B cells in response to BAFF and was critical for the upregulation of the receptor for BAFF following BCR crosslinking. Our findings reveal an important role for p110 delta in regulating B-cell responses to BAFF.