The earliest stages of B cell development require a chemokine stromal cell-derived factor/pre-B cell growth-stimulating factor.
Environmental factors essential for the first stages of B lymphopoiesis remain elusive. Here, we report that immediately after commitment to B lineage, precursors become dependent on a chemokine SDF-1 and its receptor CXCR4 using mutant and radiation chimeric mice. In bone marrow, generation of the earliest identifiable B cell precursor populations requires CXCR4. In fetal liver, we identified Lin(-)CD19(-)c-kit(+)IL-7Ralpha(+)AA4.1(+), the earliest unipotent B cell precursor population, and found that its development was severely affected in SDF-1(-/-) embryos but not in IL-7(-/-) embryos. Lin(-) T cell progenitors appeared normal in SDF-1(-/-) embryos. Moreover, SDF-1 exhibited specific biologic activities on the earliest B cell precursors. SDF-1 provides the first example of a cytokine responsible for the earliest B lineage stages.
Egawa
T
T
Department of Immunology, Research Institute, Osaka Medical Center for Maternal and Child Health, 840, Murodo-cho, Izumi, 594-1101, Osaka, Japan.
Kawabata
K
K
Kawamoto
H
H
Amada
K
K
Okamoto
R
R
Fujii
N
N
Kishimoto
T
T
Katsura
Y
Y
Nagasawa
T
T
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology; D001402:B-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation; D019070:Cell Lineage; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006413:Hematopoietic System / Q000196:embryology*; D008099:Liver / Q000196:embryology / Q000276:immunology; D008221:Lymphoid Tissue / Q000196:embryology; D051379:Mice; D008817:Mice, Mutant Strains; D019718:Receptors, CXCR4 / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4