Follicular Dendritic Cells Catalyze Hepatocyte Growth Factor (HGF) Activation in the Germinal Center Microenvironment by Secreting the Serine Protease HGF Activator
| Autor: | Richard J. Bende, Marcel Spaargaren, Anne-Pauline van Huijstee, Hiroaki Kataoka, Patrick W. B. Derksen, Steven T. Pals, Esther P. M. Tjin |
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| Přispěvatelé: | Dermatology, Amsterdam institute for Infection and Immunity, Cancer Center Amsterdam, Pathology |
| Rok vydání: | 2005 |
| Předmět: |
Lymphoma
B-Cell medicine.medical_treatment Immunology Biology Catalysis Proto-Oncogene Proteins medicine Centroblasts Humans Immunology and Allergy Receptors Growth Factor Child Receptor B cell Follicular dendritic cells Hepatocyte Growth Factor Activator (genetics) Serine Endopeptidases Germinal center Proto-Oncogene Proteins c-met Germinal Center Cell biology Cytokine medicine.anatomical_structure Hepatocyte growth factor Dendritic Cells Follicular Signal Transduction medicine.drug |
| Zdroj: | Journal of immunology (Baltimore, Md., 175(5), 2807-2813. American Association of Immunologists |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Ag-specific B cell differentiation, the process that gives rise to plasma cells and memory B cells, involves the formation of germinal centers (GC). Within the GC microenvironment, multiple steps of B cell proliferation, selection, and maturation take place, which are controlled by the BCR in concert with cytokines and contact-dependent signals from follicular dendritic cells (FDCs) and T cells. Signaling by the multifunctional cytokine hepatocyte growth factor (HGF) and its receptor MET has been shown to induce integrin-mediated adhesion of B cells to VCAM-1, which is expressed by FDCs. In the present study we have examined the expression of regulatory components of the HGF/MET pathway, including HGF activator (HGFA), within the secondary lymphoid organ microenvironment. We show that MET is expressed by both centroblasts and plasma cells, and that HGFA is expressed by plasma cells. Because we have shown that HGF is a potent growth and survival factor for malignant plasma cells, HGF may also serve as a survival factor for normal plasma cells. Furthermore, we demonstrate that FDCs are the major source for HGF and its activator within the GC microenvironment. Both HGF and HGFA are expressed by FDCs in the GC dark zone (CD21high/CD23low), but not in the light zone (CD21high/CD23high). These findings suggest that HGF and HGFA provided by dark zone FDCs help to regulate the proliferation, survival, and/or adhesion of MET-positive centroblasts. |
| Databáze: | OpenAIRE |
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