Most adaptive immune responses require the activation of specific T cells through the T cell antigen receptor (TCR)-CD3 complex. Here we show that cholesterol sulfate (CS), a naturally occurring analog of cholesterol, inhibits CD3 ITAM phosphorylation, a crucial first step in T cell activation. In biochemical studies, CS disrupted TCR multimers, apparently by displacing cholesterol, which is known to bind TCRβ. Moreover,九寨溝旅遊, CS-deficient mice showed heightened sensitivity to a self-antigen, whereas increasing CS content by intrathymic injection inhibited thymic selection, indicating that this molecule is an intrinsic regulator of thymocyte development. These results reveal a regulatory role for CS in TCR signaling and thymic selection, highlighting the importance of the membrane microenvironment in modulating cell surface receptor activation.
之後,作者通過流感病毒感染模型,証明流感病毒特異性的記憶B細胞的分化需要依賴BACH2的活性。而如果人為地抑制BACH2的活性,則會抑制GC B細胞向記憶B細胞分化。(生物穀Bioon.com)
2016年6月24日 訊 /生物穀BIOON/ --體液免疫依賴於記憶B細胞以及長存活期的傚應B細胞(漿細胞)的發育,儘筦一些記憶B細胞在生發中心形成以前,經過T-B細胞的初次互作就能夠產生,縫雙眼皮推薦,但大部分記憶B細胞依賴於淋巴結的生發中心。
Feng Wang, Katharina Beck-García, Carina Zorzin, Wolfgang W A Schamel & Mark M Davis