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  • Title: Notch ligands expressed by follicular dendritic cells protect germinal center B cells from apoptosis.
    Author: Yoon SO, Zhang X, Berner P, Blom B, Choi YS.
    Journal: J Immunol; 2009 Jul 01; 183(1):352-8. PubMed ID: 19542446.
    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.
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