title: Notch ligands expressed by follicular dendritic cells protect germinal center B cells from apoptosis.
abstract: The Notch signaling pathway is one of the most conserved mechanisms to regulate cell fate in many tissues during development and postnatal life. In the immune system, Notch signaling regulates T and B cell development and modulates the differentiation of T and B cells. In this study, we investigated the functional roles of Notch signaling in human B cell differentiation within the germinal center (GC). Notch ligands, Delta-like 1 (Dll1) and Jagged 1 (Jg1), are expressed by follicular dendritic cells (FDC) but not by B cells in the GC, while GC-B cells express the Notch receptors, Notch1 and Notch2. The blockade of Notch signaling pathways using a gamma-secretase inhibitor, DAPT (N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester), reduces the survival of GC-B cells in the presence of FDC/HK cells. Jg1 has a dominant effect on GC-B cell survival mediated by Notch signaling. Furthermore, Notch cooperates with another anti-apoptotic factor, BAFF/Blys produced by FDC to support GC-B cell growth. Taken together, our data shows the important role of Notch signaling provided by FDC in the survival of GC-B cells in vitro.
authors: Ochsner Clinic Foundation, New Orleans, LA 70121, USA.
authors: Sun-Ok
authors: SO
authors: Yoon
authors: Xin
authors: X
authors: Zhang
authors: Paul
authors: P
authors: Berner
authors: Bianca
authors: B
authors: Blom
authors: Yong Sung
authors: YS
authors: Choi
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D020566:Dendritic Cells, Follicular / Q000276:immunology* / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D051883:Receptor, Notch2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
chemical_list: D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D004151:Dipeptides; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; C497761:NOTCH1 protein, human; C497764:NOTCH2 protein, human; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D000072099:Serrate-Jagged Proteins