The chemokine SDF-1, stromal cell-derived factor 1, attracts early stage B cell precursors via the chemokine receptor CXCR4.
In the bone marrow, progenitor (pro-) and precursor (pre-) B cells depend on close contact with stromal cells for growth and maturation. Stromal cell-derived factor 1 (SDF-1), also known as pre-B cell growth-stimulating factor, is produced by bone marrow stromal cells and was reported to act together with interleukin-7 as co-mitogen for pre-B cells. SDF-1 was recently shown to be a chemokine which is chemotactic for different types of leukocytes and acts via the chemokine receptor CXCR4. Using sorted B220+ bone marrow cells and several B cell lines characteristic for different stages of B lymphopoiesis, we now show that SDF-1 is a potent attractant for pro- and pre-B cells, but is inactive on B cells at later stages of development. In early B cell precursors, SDF-1 induced intracellular Ca2+ mobilization and in vitro migration with a potency and efficacy similar to that observed for chemokines acting on blood leukocytes. These responses were mediated via CXCR4 as they could be inhibited by an antireceptor antibody. SDF-1 is the first chemokine shown to act on early-stage B cell precursors. Mice lacking SDF-1 die perinatally and show a severe deficiency in B lymphopoiesis. We propose that SDF-1 released from the stromal cells exerts its critical hematopoietic function by selectively attracting and confining early B cell precursors within the bone marrow microenvironment that provides the necessary factors for growth and differentiation.
D'Apuzzo
M
M
Theodor-Kocher Institute, University of Bern, Switzerland. dapuzzo@tki.unibe.ch
Rolink
A
A
Loetscher
M
M
Hoxie
J A
JA
Clark-Lewis
I
I
Melchers
F
F
Baggiolini
M
M
Moser
B
B
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells; D002460:Cell Line; D054377:Chemokine CXCL12; D018925:Chemokines / Q000378:metabolism / Q000502:physiology*; D019743:Chemokines, CXC; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019718:Receptors, CXCR4; D015728:Receptors, HIV / Q000502:physiology*; D017154:Stromal Cells / Q000378:metabolism
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D008565:Membrane Proteins; D019718:Receptors, CXCR4; D015728:Receptors, HIV; D017493:Leukocyte Common Antigens; D019204:GTP-Binding Proteins