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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Artificial Gene Fusion
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B-Lymphocytes / cytology*
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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Basic Helix-Loop-Helix Transcription Factors
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Calcium-Binding Proteins
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Cell Differentiation / immunology
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Cell Lineage / immunology
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Endothelial Cells / cytology
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Endothelial Cells / immunology*
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Glucosyltransferases
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Glycosyltransferases / deficiency
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Glycosyltransferases / genetics
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Glycosyltransferases / immunology
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Glycosyltransferases / metabolism*
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Homeodomain Proteins
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Intercellular Signaling Peptides and Proteins / metabolism*
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Mice
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Mice, Knockout
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Proteins / genetics
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Proteins / immunology
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Proteins / metabolism*
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RNA, Messenger / genetics
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Receptor, Notch2 / metabolism
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Spleen / cytology
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Spleen / immunology*
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Spleen / metabolism
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Transcription Factor HES-1
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Calcium-Binding Proteins
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Dlk1 protein, mouse
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Hes1 protein, mouse
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Homeodomain Proteins
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Intercellular Signaling Peptides and Proteins
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Proteins
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RNA, Messenger
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Receptor, Notch2
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Transcription Factor HES-1
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Glycosyltransferases
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Glucosyltransferases
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Lfng protein, mouse
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Mfng protein, mouse