The Earliest Stages of B Cell Development Require a Chemokine Stromal Cell-Derived Factor/Pre-B Cell Growth-Stimulating Factor

• Published in: Immunity (Cambridge, Mass.) Vol. 15; no. 2; pp. 323 - 334
• Main Authors: Egawa, Takeshi, Kawabata, Kenji, Kawamoto, Hiroshi, Amada, Kei, Okamoto, Rika, Fujii, Nobutaka, Kishimoto, Tadamitsu, Katsura, Yoshimoto, Nagasawa, Takashi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2001
• Subjects: Animals; B-Lymphocyte Subsets - cytology; B-Lymphocytes - cytology; Cell Differentiation; Cell Lineage; Chemokine CXCL12; Chemokines, CXC - metabolism; CXCR4 protein; Hematopoiesis; Hematopoietic Stem Cells - cytology; Hematopoietic System - embryology; Liver - embryology; Liver - immunology; Lymphoid Tissue - embryology; Mice; Mice, Mutant Strains; Receptors, CXCR4 - metabolism; SDF-1 protein; Stromal Cells - metabolism
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(01)00185-6

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.