Chemokines are a family of small structurally related molecules that were recognized originally for their ability to regulate cell trafficking in inflammation. We have found that a chemokine, CXC chemokine ligand 12/stromal cell-derived factor/pre-B-cell growth stimulating factor (CXCL12/ SDF-1/PBSF) and its physiologic receptor CXCR4 are essential for hematopoiesis including B lymphocyte development and colonization of bone marrow by hematopoietic cells including hematopoietic stem cells (HSCs) during ontogeny as well as cardiovascular formation. Recently, we have shown that a small population of reticular stromal cells, which has high levels of CXCL12 expression, termed CXCL12-abundant reticular (CAR) cells have several long processes and are scattered throughout adult bone marrow. In addition, most of the earliest B cell precursors, pre-pro-B cells and end-stage B cells, plasma cells, which require CXCL12, as well as primitive hematopoietic progenitors were attached to the CAR cells. These results suggest that the CAR cells function as cellular niches for B-cell development and that CXCL12 plays a role in maintaining the blood cells in the niches. It has been hypothesized that osteoprogenitors reside in the stromal tissues of bone marrow and play an important role in hematopoiesis. The nature and functions of CAR cells are important issues for the future.
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References
Ara, T., K. Tokoyoda, T. Sugiyama, T. Egawa, K. Kawabata, and T. Nagasawa. 2003. Long-term hematopoietic stem cells require stromal cell-derived factor-1 for colonizing bone marrow during ontogeny. Immunity 19: 257–267.
Arai, F., A. Hirao, M. Ohmura, et al. 2004. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell 118: 149–161.
Baggiolini, M., B. Dewald, and B. Moser. 1997. Human chemokines: an update. Annu Rev Immunol 15: 675–705.
Bleul, C.C., R.C. Fuhlbrigge, J.M. Casasnovas, A. Aiuti, and T.A. Springer. 1996. A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1). J Exp Med 184: 1101–1109.
Calvi, L.M., G.B. Adams, K.W. Weibrecht, et al. 2003. Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425: 841–846.
Egawa, T., K. Kawabata, H. Kawamoto, et al. 2001. The earliest stages of B cell development require a chemokine stromal cell-derived factor/pre-B cell growth-stimulating factor. Immunity 15: 323–334.
Hardy, R.R., C.E. Carmack, S.A. Shinton, J.D. Kemp, and K. Hayakawa. 1991 Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow. J Exp Med 173: 1213–1225.
Hargreaves, D.C., P.L. Hyman, T.T. Lu, et al. 2001. Links A coordinated change in chemokine responsiveness guides plasma cell movements. J Exp Med 194: 45–56.
Hirose, J., T. Kouro, H. Igarashi, et al. 2002. A developing picture of lymphopoiesis in bone marrow. Immunol Rev 189: 28–40.
Jacobsen, K., J. Kravitz, P.W. Kincade, and D.G. Osmond. 1996. Adhesion receptors on bone marrow stromal cells: in vivo expression of vascular cell adhesion molecule-1 by reticular cells and sinusoidal endothelium in normal and gamma-irradiated mice. Blood 87: 73–82.
Kiel, M.J., O.H. Yilmaz, T. Iwashita, et al. 2005. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121: 1109–1121.
Lieberam, I., D. Agalliu, T. Nagasawa, J. Ericson, and T.M. Jessell. 2005. A Cxcl12-CXCR4 chemokine signaling pathway defines the initial trajectory of mammalian motor axons. Neuron 47: 667–679.
Lord, B.I., N.G. Testa, and J.H. Hendry. 1975. The relative spatial distributions of CFUs and CFUc in the normal mouse femur. Blood 46: 65–72.
Ma, Q., D. Jones, and T. Springer. 1999. The chemokine receptor CXCR4 is required for the retention of B lineage and granulocytic precursors within the bone marrow microenvironment. Immunity 10: 463–471.
Nagasawa, T. 2006. Microenvironmental niches in the bone marrow for B-cell development. Nat Rev Immunol 6: 107–116.
Nagasawa, T., H. Kikutani, and T. Kishimoto. 1994. Molecular cloning and structure of a pre-B-cell growth-stimulating factor. Proc Natl Acad Sci USA 91: 2305–2309.
Nagasawa, T., S. Hirota, K. Tachibana, et al. 1996. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 382: 635–638.
Nie, Y., J. Waite, F. Brewer, et al. 2004. The role of CXCR4 in maintaining peripheral B cell compartments and humoral immunity. J Exp Med 200: 1145–1156.
Peled, A., I. Petit, O. Kollet, et al. 1999. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 283: 845–848.
Raz, E. 2003. Primordial germ cell development: The zebrafish perspective. Nat Rev Genet 4: 690–700.
Rouleau, M.F., J. Mitchell, and D. Goltzman. 1990. Characterization of the major parathyroid hormone target cell in the endosteal metaphysis of rat long bones. J Bone Miner Res 5: 1043–1053.
Tachibana, K., S. Hirota, H. Iizasa, et al. 1998. The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature 393: 591–594.
Tashiro, K., H. Tada, R. Heilker, et al. 1993. Signal sequence trap: a cloning strategy for secreted proteins and type I membrane proteins. Science 261: 600–603.
Tokoyoda, K., T. Egawa, T. Sugiyama, B.I. Choi, and T. Nagasawa. 2004. Cellular niches controlling B lymphocyte behavior within bone marrow during development. Immunity 20: 707–718.
Tran, P.B., and R.J. Miller. 2003. Chemokine receptors: signposts to brain development and disease. Nat Rev Neurosci 4: 444–455.
Visnjic, D., Z. Kalajzic, D.W. Rowe, et al. 2004. Hematopoiesis is severely altered in mice with an induced osteoblast deficiency. Blood 103: 3258–3264.
Zhang, J., C. Niu, L. Ye, et al. 2003. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425: 836–841.
Zou, Y.R., A.H. Kottmann, M. Kuroda, I. Taniuchi, and D.R. Littman. 1998. Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 393: 595–599.
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Nagasawa, T. (2007). The Chemokine CXCL12 and Regulation of Hsc and B Lymphocyte Development in the Bone Marrow Niche. In: Choi, Y. (eds) Osteoimmunology. Advances in Experimental Medicine and Biology, vol 602. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-72009-8_9
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