Henley Thomas, Kovesdi Dorottya, Turner Martin
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK.
Eur J Immunol. 2008 Dec;38(12):3543-8. doi: 10.1002/eji.200838618.
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 P110delta. We find that the loss of P110delta 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. P110delta 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 p110delta in regulating B-cell responses to BAFF.
肿瘤坏死因子家族的B细胞活化因子（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人们所了解。最近有证据表明PI3K/Akt信号通路在对BAFF的反应中发挥作用。然而，PI3K家族对BAFF信号传导的重要性以及PI3K功能丧失对BAFF反应的影响仍然未知。因此，我们研究了缺乏PI3K催化亚基P110δ的B细胞对BAFF的反应。我们发现P110δ的缺失损害了BAFF介导的培养B细胞的存活，表明PI3K家族的这一成员在调节B细胞对BAFF反应的存活中具有直接作用。P110δ是B细胞对BAFF反应生长所必需的，并且对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反应中的重要作用。
