Otipoby Kevin L, Waisman Ari, Derudder Emmanuel, Srinivasan Lakshmi, Franklin Andrew, Rajewsky Klaus
Immune Disease Institute, Harvard Medical School, Boston, MA 02115;
Institute for Genetics, University of Cologne, 50674 Cologne, Germany;
Proc Natl Acad Sci U S A. 2015 Sep 29;112(39):12145-50. doi: 10.1073/pnas.1516428112. Epub 2015 Sep 14.
B cells respond to antigens by engagement of their B-cell antigen receptor (BCR) and of coreceptors through which signals from helper T cells or pathogen-associated molecular patterns are delivered. We show that the proliferative response of B cells to the latter stimuli is controlled by BCR-dependent activation of phosphoinositidyl 3-kinase (PI-3K) signaling. Glycogen synthase kinase 3β and Foxo1 are two PI-3K-regulated targets that play important roles, but to different extents, depending on the specific mitogen. These results suggest a model for integrating signals from the innate and the adaptive immune systems in the control of the B-cell immune response.
B细胞通过其B细胞抗原受体(BCR)和共受体与抗原结合来做出反应,辅助性T细胞的信号或病原体相关分子模式通过这些共受体传递。我们发现,B细胞对后一种刺激的增殖反应受磷酸肌醇3激酶(PI-3K)信号通路的BCR依赖性激活控制。糖原合酶激酶3β和Foxo1是两个受PI-3K调节的靶点,它们发挥着重要作用,但程度不同,这取决于特定的促细胞分裂剂。这些结果提示了一个在B细胞免疫反应控制中整合来自先天免疫系统和适应性免疫系统信号的模型。