PMID- 9182684
OWN - NLM
STAT- MEDLINE
DCOM- 19970717
LR  - 20190508
IS  - 0022-1007 (Print)
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Linking)
VI  - 185
IP  - 12
DP  - 1997 Jun 16
TI  - Paracrine regulation of germinal center B cell adhesion through the 
      c-met-hepatocyte growth factor/scatter factor pathway.
PG  - 2121-31
AB  - 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.
FAU - van der Voort, R
AU  - van der Voort R
AD  - Department of Pathology, Academic Medical Center, University of Amsterdam, 1105 
      AZ Amsterdam, The Netherlands.
FAU - Taher, T E
AU  - Taher TE
FAU - Keehnen, R M
AU  - Keehnen RM
FAU - Smit, L
AU  - Smit L
FAU - Groenink, M
AU  - Groenink M
FAU - Pals, S T
AU  - Pals ST
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Fibronectins)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - B-Lymphocytes/*physiology
MH  - Cell Adhesion
MH  - Fibronectins/physiology
MH  - Germinal Center/*physiology
MH  - Hepatocyte Growth Factor/*physiology
MH  - Humans
MH  - Mice
MH  - Proto-Oncogene Proteins c-met
MH  - Receptor Protein-Tyrosine Kinases/*physiology
MH  - Tumor Cells, Cultured
MH  - Vascular Cell Adhesion Molecule-1/physiology
PMC - PMC2196350
EDAT- 1997/06/16 00:00
MHDA- 1997/06/16 00:01
PMCR- 1997/12/16
CRDT- 1997/06/16 00:00
PHST- 1997/06/16 00:00 [pubmed]
PHST- 1997/06/16 00:01 [medline]
PHST- 1997/06/16 00:00 [entrez]
PHST- 1997/12/16 00:00 [pmc-release]
AID - 10.1084/jem.185.12.2121 [doi]
PST - ppublish
SO  - J Exp Med. 1997 Jun 16;185(12):2121-31. doi: 10.1084/jem.185.12.2121.