Differences in CXCR4-mediated signaling in B cells.
Among all chemokine receptors CXCR4 possesses a unique response profile and distinguishes itself through a prolonged signaling capacity. Here, we investigated the signaling capacity of CXCR4 to its so far known unique ligand CXCL12 in B cell lines and primary CD19(+) B lymphocytes. During lymphopoiesis, CXCR4 is continuously expressed on the surface of B cells. However, its signaling profile changes inasmuch preB and proB cells migrate towards CXCL12, mobilize intracellular calcium and activate the small GTPases Rac1 and Cdc42, whereas mature B cells do not show these responses, albeit the cells retain the capability to migrate in response to CXCL13 and CCL21. By contrast, stimulation of B cells with CXCL12 at all stages of development results in the activation of the MAP-kinase cascade and in rapid CXCR4 internalization. The pathways leading to ERK1/2 activation are different in preB and mature B cell lines. In either case, ERK1/2 activation is pertussis toxin sensitive, but only in mature B-cells inhibition of PI3-kinase causes an almost complete block of ERK1/2 activation. Taken together, the results show that CXCR4 changes its coupling to downstream signal-transduction pathways in B cells, suggesting that receptor activity may depend on accessory proteins.
Palmesino
Elena
E
Institute for Research in Biomedicine, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
Moepps
Barbara
B
Gierschik
Peter
P
Thelen
Marcus
M
D018941:Antigens, CD19 / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D020013:Calcium Signaling; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D006801:Humans; D038041:Lymphopoiesis; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction
D018941:Antigens, CD19; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3