Lunatic and manic fringe cooperatively enhance marginal zone B cell precursor competition for delta-like 1 in splenic endothelial niches

Joanne B Tan; Keli Xu; Kira Cretegny; Ioana Visan; Julie S Yuan; Sean E Egan; Cynthia J Guidos

doi:10.1016/j.immuni.2008.12.016

Lunatic and manic fringe cooperatively enhance marginal zone B cell precursor competition for delta-like 1 in splenic endothelial niches

Immunity. 2009 Feb 20;30(2):254-63. doi: 10.1016/j.immuni.2008.12.016. Epub 2009 Feb 12.

Authors

Joanne B Tan¹, Keli Xu, Kira Cretegny, Ioana Visan, Julie S Yuan, Sean E Egan, Cynthia J Guidos

Affiliation

¹ Hospital for Sick Children Research Institute, Toronto, ON, Canada.

PMID: 19217325
DOI: 10.1016/j.immuni.2008.12.016

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Artificial Gene Fusion
B-Lymphocytes / cytology*
B-Lymphocytes / immunology*
B-Lymphocytes / metabolism
Basic Helix-Loop-Helix Transcription Factors
Calcium-Binding Proteins
Cell Differentiation / immunology
Cell Lineage / immunology
Endothelial Cells / cytology
Endothelial Cells / immunology*
Glucosyltransferases
Glycosyltransferases / deficiency
Glycosyltransferases / genetics
Glycosyltransferases / immunology
Glycosyltransferases / metabolism*
Homeodomain Proteins
Intercellular Signaling Peptides and Proteins / metabolism*
Mice
Mice, Knockout
Proteins / genetics
Proteins / immunology
Proteins / metabolism*
RNA, Messenger / genetics
Receptor, Notch2 / metabolism
Spleen / cytology
Spleen / immunology*
Spleen / metabolism
Transcription Factor HES-1

Substances

Basic Helix-Loop-Helix Transcription Factors
Calcium-Binding Proteins
Dlk1 protein, mouse
Hes1 protein, mouse
Homeodomain Proteins
Intercellular Signaling Peptides and Proteins
Proteins
RNA, Messenger
Receptor, Notch2
Transcription Factor HES-1
Glycosyltransferases
Glucosyltransferases
Lfng protein, mouse
Mfng protein, mouse