title: Lunatic and manic fringe cooperatively enhance marginal zone B cell precursor competition for delta-like 1 in splenic endothelial niches.
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.
authors.affiliation: Hospital for Sick Children Research Institute, Toronto, ON, Canada.
authors.forename: Joanne B
authors.initials: JB
authors.lastname: Tan
authors.forename: Keli
authors.initials: K
authors.lastname: Xu
authors.forename: Kira
authors.initials: K
authors.lastname: Cretegny
authors.forename: Ioana
authors.initials: I
authors.lastname: Visan
authors.forename: Julie S
authors.initials: JS
authors.lastname: Yuan
authors.forename: Sean E
authors.initials: SE
authors.lastname: Egan
authors.forename: Cynthia J
authors.initials: CJ
authors.lastname: Guidos
mesh_terms: D000818:Animals; D019677:Artificial Gene Fusion; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology*; D005964:Glucosyltransferases; D016695:Glycosyltransferases / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051883:Receptor, Notch2 / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D005964:Glucosyltransferases; D016695:Glycosyltransferases; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D051883:Receptor, Notch2; D000072056:Transcription Factor HES-1; C512925:Dlk1 protein, mouse; C489734:Hes1 protein, mouse; C498392:Lfng protein, mouse; C486343:Mfng protein, mouse