Paracrine Regulation of Germinal Center B Cell Adhesion through the c-Met–Hepatocyte Growth Factor/Scatter Factor Pathway
T cell–dependent humoral immune responses are initiated by the activation of naive B cells in the T cell areas of the secondary lymphoid tissues. This primary B cell activation leads to migration of germinal center (GC) cell precursors into B cell follicles where they engage follicular dendritic cel...
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| Format: | Online |
| Language: | English |
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The Rockefeller University Press
1997
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196350/ |
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pubmed-2196350 |
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pubmed-21963502008-04-16 Paracrine Regulation of Germinal Center B Cell Adhesion through the c-Met–Hepatocyte Growth Factor/Scatter Factor Pathway van der Voort, Robbert Taher, Taher E.I. Keehnen, Robert M.J. Smit, Lia Groenink, Martijn Pals, Steven T. Article T cell–dependent humoral immune responses are initiated by the activation of naive B cells in the T cell areas of the secondary lymphoid tissues. This primary B cell activation leads to migration of germinal center (GC) cell precursors into B cell follicles where they engage follicular dendritic cells (FDC) and T cells, and differentiate into memory B cells or plasma cells. Both B cell migration and interaction with FDC critically depend on integrin-mediated adhesion. To date, the physiological regulators of this adhesion were unkown. In the present report, we have identified the c-met–encoded receptor tyrosine kinase and its ligand, the growth and motility factor hepatocyte growth factor/scatter factor (HGF/SF), as a novel paracrine signaling pathway regulating B cell adhesion. We observed that c-Met is predominantly expressed on CD38+CD77+ tonsillar B cells localized in the dark zone of the GC (centroblasts). On tonsil B cells, ligation of CD40 by CD40-ligand, induces a transient strong upregulation of expression of the c-Met tyrosine kinase. Stimulation of c-Met with HGF/SF leads to receptor phosphorylation and, in addition, to enhanced integrin-mediated adhesion of B cells to both VCAM-1 and fibronectin. Importantly, the c-Met ligand HGF/SF is produced at high levels by tonsillar stromal cells thus providing signals for the regulation of adhesion and migration within the lymphoid microenvironment. The Rockefeller University Press 1997-06-16 /pmc/articles/PMC2196350/ /pubmed/9182684 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
van der Voort, Robbert Taher, Taher E.I. Keehnen, Robert M.J. Smit, Lia Groenink, Martijn Pals, Steven T. |
| spellingShingle |
van der Voort, Robbert Taher, Taher E.I. Keehnen, Robert M.J. Smit, Lia Groenink, Martijn Pals, Steven T. Paracrine Regulation of Germinal Center B Cell Adhesion through the c-Met–Hepatocyte Growth Factor/Scatter Factor Pathway |
| author_facet |
van der Voort, Robbert Taher, Taher E.I. Keehnen, Robert M.J. Smit, Lia Groenink, Martijn Pals, Steven T. |
| author_sort |
van der Voort, Robbert |
| title |
Paracrine Regulation of Germinal Center B Cell Adhesion through the c-Met–Hepatocyte Growth Factor/Scatter Factor Pathway |
| title_short |
Paracrine Regulation of Germinal Center B Cell Adhesion through the c-Met–Hepatocyte Growth Factor/Scatter Factor Pathway |
| title_full |
Paracrine Regulation of Germinal Center B Cell Adhesion through the c-Met–Hepatocyte Growth Factor/Scatter Factor Pathway |
| title_fullStr |
Paracrine Regulation of Germinal Center B Cell Adhesion through the c-Met–Hepatocyte Growth Factor/Scatter Factor Pathway |
| title_full_unstemmed |
Paracrine Regulation of Germinal Center B Cell Adhesion through the c-Met–Hepatocyte Growth Factor/Scatter Factor Pathway |
| title_sort |
paracrine regulation of germinal center b cell adhesion through the c-met–hepatocyte growth factor/scatter factor pathway |
| description |
T cell–dependent humoral immune responses are initiated by the activation of naive B cells in the T cell areas of the secondary lymphoid tissues. This primary B cell activation leads to migration of germinal center (GC) cell precursors into B cell follicles where they engage follicular dendritic cells (FDC) and T cells, and differentiate into memory B cells or plasma cells. Both B cell migration and interaction with FDC critically depend on integrin-mediated adhesion. To date, the physiological regulators of this adhesion were unkown. In the present report, we have identified the c-met–encoded receptor tyrosine kinase and its ligand, the growth and motility factor hepatocyte growth factor/scatter factor (HGF/SF), as a novel paracrine signaling pathway regulating B cell adhesion. We observed that c-Met is predominantly expressed on CD38+CD77+ tonsillar B cells localized in the dark zone of the GC (centroblasts). On tonsil B cells, ligation of CD40 by CD40-ligand, induces a transient strong upregulation of expression of the c-Met tyrosine kinase. Stimulation of c-Met with HGF/SF leads to receptor phosphorylation and, in addition, to enhanced integrin-mediated adhesion of B cells to both VCAM-1 and fibronectin. Importantly, the c-Met ligand HGF/SF is produced at high levels by tonsillar stromal cells thus providing signals for the regulation of adhesion and migration within the lymphoid microenvironment. |
| publisher |
The Rockefeller University Press |
| publishDate |
1997 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196350/ |
| _version_ |
1611432562389942272 |