Hobeika Elias, Levit-Zerdoun Ella, Anastasopoulou Vasiliki, Pohlmeyer Roland, Altmeier Simon, Alsadeq Ameera, Dobenecker Marc-Werner, Pelanda Roberta, Reth Michael
Max-Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany Department of Molecular Immunology, BioIII, Faculty of Biology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany
Max-Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
EMBO J. 2015 Apr 1;34(7):925-39. doi: 10.15252/embj.201489732. Epub 2015 Jan 28.
The development and function of B lymphocytes is regulated by numerous signaling pathways, some emanating from the B-cell antigen receptor (BCR). The spleen tyrosine kinase (Syk) plays a central role in the activation of the BCR, but less is known about its contribution to the survival and maintenance of mature B cells. We generated mice with an inducible and B-cell-specific deletion of the Syk gene and found that a considerable fraction of mature Syk-negative B cells can survive in the periphery for an extended time. Syk-negative B cells are defective in BCR, RP105 and CD38 signaling but still respond to an IL-4, anti-CD40, CpG or LPS stimulus. Our in vivo experiments show that Syk-deficient B cells require BAFF receptor and CD19/PI3K signaling for their long-term survival. These studies also shed a new light on the signals regulating the maintenance of the normal mature murine B-cell pool.
B淋巴细胞的发育和功能受众多信号通路调控，其中一些信号通路源自B细胞抗原受体（BCR）。脾酪氨酸激酶（Syk）在BCR激活过程中起核心作用，但对于其在成熟B细胞存活和维持中的作用却知之甚少。我们构建了可诱导且B细胞特异性缺失Syk基因的小鼠，发现相当一部分成熟的Syk阴性B细胞能够在外周存活较长时间。Syk阴性B细胞在BCR、RP105和CD38信号传导方面存在缺陷，但仍能对IL-4、抗CD40、CpG或LPS刺激作出反应。我们的体内实验表明，Syk缺陷型B细胞的长期存活需要BAFF受体和CD19/PI3K信号传导。这些研究也为调节正常成熟小鼠B细胞库维持的信号传导提供了新的见解。
