Lunatic and Manic Fringe Cooperatively Enhance Marginal Zone B Cell Precursor Competition for Delta-like 1 in Splenic Endothelial Niches

Hospital for Sick Children Research Institute, Toronto, ON, Canada.
Immunity (Impact Factor: 19.75). 03/2009; 30(2):254-63. DOI: 10.1016/j.immuni.2008.12.016
Source: PubMed

ABSTRACT 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.

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