Tan Joanne B, Xu Keli, Cretegny Kira, Visan Ioana, Yuan Julie S, Egan Sean E, Guidos Cynthia J
Hospital for Sick Children Research Institute, Toronto, ON, Canada.
Immunity. 2009 Feb 20;30(2):254-63. doi: 10.1016/j.immuni.2008.12.016. Epub 2009 Feb 12.
Notch2 activation induced by Delta-like-1 (DL1) drives development of splenic marginal zone (MZ) B cells, an innate-like lineage that protects against sepsis. DL1 interacts with Notch2 weakly, but it is not known whether enhancement of DL1-induced Notch2 activation by Fringe glycosyltransferases is important for MZ B cell development. Furthermore, DL1-expressing cells that promote MZ B cell development have not been identified. We show that Lunatic Fringe (Lfng) and Manic Fringe (Mfng) cooperatively enhanced the DL1-Notch2 interaction to promote MZ B cell development. We also identified radio-resistant red pulp endothelial cells in the splenic MZ that express high amounts of DL1 and promoted MZ B generation. Finally, MZ B cell precursor competition for DL1 homeostatically regulated entry into the MZ B cell pool. Our study has revealed that the Fringe-Notch2 interaction has important functions in vivo and provides insights into mechanisms regulating MZ B cell development.
由Delta样-1（DL1）诱导的Notch2激活驱动脾脏边缘区（MZ）B细胞的发育，MZ B细胞是一种可抵御败血症的固有样细胞谱系。DL1与Notch2的相互作用较弱，但尚不清楚边缘区糖基转移酶增强DL1诱导的Notch2激活对MZ B细胞发育是否重要。此外，促进MZ B细胞发育的表达DL1的细胞尚未被鉴定出来。我们发现， Lunatic Fringe（Lfng）和Manic Fringe（Mfng）协同增强DL1与Notch2的相互作用，以促进MZ B细胞发育。我们还在脾脏MZ中鉴定出了抗辐射的红髓内皮细胞，这些细胞表达大量的DL1并促进MZ B细胞的生成。最后，MZ B细胞前体对DL1的竞争稳态调节了进入MZ B细胞池的过程。我们的研究表明，Fringe与Notch2的相互作用在体内具有重要功能，并为调节MZ B细胞发育的机制提供了见解。
