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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3706-3712.
Prepublished online as a Blood First Edition Paper on January 16, 2007; DOI 10.1182/blood-2006-08-041384.
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Submitted August 15, 2006
Accepted October 18, 2006
Osteoblasts support B lymphocyte commitment and differentiation from hematopoietic stem cells
Jiang Zhu, Russell Garrett, Younghun Jung, Yi Zhang, Nacksung Kim, Jianhua Wang, Gerard J. Joe, Elizabeth Hexner, Yongwon Choi, Russell Taichman, and Stephen G. Emerson*
Departments of Medicine, Pathology and Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, United States
Department of Periodontics, Prevention & Geriatrics, University of Michigan School of Dentistry, Ann Arbor, MI, United States
Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA, United States
* Corresponding author; email: emersons{at}mail.med.upenn.edu.
Early B lymphopoiesis in mammals is induced within the bone marrow (BM) microenvironment, but which cells constitute this niche is not known. Previous studies had shown that osteoblasts (OB) support hematopoietic stem cell proliferation and myeloid differentiation. We now find that purified primary murine OB also support the differentiation of primitive hematopoietic stem cells through lymphoid commitment and subsequent differentiation to all stages of B cell precursors and mature B cells. Lin-Sca-1+Rag-2- BM cell differentiation requires attachment to OB to B cells in vitro, and this developmental process is mediated via VCAM-1, SDF-1 and IL-7 signaling induced by parathyroid hormone (PTH). Addition of cytokines produced by non-osteoblastic stromal cells (c-kit ligand, Il-6, and IL-3) shifted the cultures towards myelopoiesis. Confirming the role of OB in B lymphopoiesis, we found that selective elimination of osteoblasts in Col2.3 -TK transgenic mice severely depleted pre-pro-B and pro-B cells from BM, preceding any decline in HSCs. Taken together, these results demonstrate that osteoblasts are both necessary and sufficient for murine B cell commitment and maturation, and thereby constitute the cellular homologue of the avian Bursa of Fabricius.

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