434회 The functional roles of Notch signaling in human B cell different…

434회 

연사:  윤 선 옥, Ochsner Clinic Foundation, New Orleans

제목:  The functional roles of Notch signaling in human B cell differentiation and B lymphomagenesis

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. Here, 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 γ-secretase inhibitor, DAPT 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. This study was extended to Non-Hodgkin’s B lymphomas most of which are originated from the GC. Similar to their normal counterpart, GC-B cells, transformed B cells are dependent on FDC for survival and proliferation in early stages. Notch signals presented by FDC to B lymphoma cells enhanced B lymphoma growth. Furthermore, Notch signals provided by FDC confer drug resistance to B lymphomas. The results obtained from our investigation would lead to the discovery of a new therapeutic strategy to relapsed B lymphomas by targeting pro-survival factors from the microenvironment as well as tumor cell itself.