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

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.

Pubmed ID: 19217325

Authors

  • Tan JB
  • Xu K
  • Cretegny K
  • Visan I
  • Yuan JS
  • Egan SE
  • Guidos CJ

Journal

Immunity

Publication Data

February 20, 2009

Associated Grants

None

Mesh Terms

  • Animals
  • Artificial Gene Fusion
  • B-Lymphocytes
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation
  • Cell Lineage
  • Endothelial Cells
  • Glycosyltransferases
  • Homeodomain Proteins
  • Intercellular Signaling Peptides and Proteins
  • Mice
  • Mice, Knockout
  • Proteins
  • RNA, Messenger
  • Receptor, Notch2
  • Spleen