Division of Immune Cell Biology, MRC National Institute for Medical Research, London NW7 1AA, UK.
Immunity. 2013 Mar 21;38(3):475-88. doi: 10.1016/j.immuni.2012.11.015. Epub 2013 Feb 28.
Follicular B cell survival requires signaling from BAFFR, a receptor for BAFF and the B cell antigen receptor (BCR). This "tonic" BCR survival signal is distinct from that induced by antigen binding and may be ligand-independent. We show that inducible inactivation of the Syk tyrosine kinase, a key signal transducer from the BCR following antigen binding, resulted in the death of most follicular B cells because Syk-deficient cells were unable to survive in response to BAFF. Genetic rescue studies demonstrated that Syk transduces BAFFR survival signals via ERK and PI3 kinase. Surprisingly, BAFFR signaling directly induced phosphorylation of both Syk and the BCR-associated Igα signaling subunit, and this Syk phosphorylation required the BCR. We conclude that the BCR and Igα may be required for B cell survival because they function as adaptor proteins in a BAFFR signaling pathway leading to activation of Syk, demonstrating previously unrecognized crosstalk between the two receptors.
滤泡 B 细胞的存活需要来自 BAFFR 的信号，BAFFR 是 BAFF 和 B 细胞抗原受体（BCR）的受体。这种“基础”BCR 存活信号不同于抗原结合诱导的信号，并且可能是配体非依赖性的。我们表明，诱导性失活 Syk 酪氨酸激酶，这是抗原结合后 BCR 的关键信号转导物，导致大多数滤泡 B 细胞死亡，因为 Syk 缺陷细胞无法响应 BAFF 而存活。遗传挽救研究表明，Syk 通过 ERK 和 PI3 激酶转导 BAFFR 存活信号。令人惊讶的是，BAFFR 信号直接诱导 Syk 和与 BCR 相关的 Igα 信号亚基的磷酸化，并且这种 Syk 磷酸化需要 BCR。我们得出结论，BCR 和 Igα 可能是 B 细胞存活所必需的，因为它们在导致 Syk 激活的 BAFFR 信号通路中作为衔接蛋白起作用，这表明两个受体之间存在以前未被认识到的串扰。
