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-7Rα⁺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.