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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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HEMATOPOIESIS
Osteoblasts support B-lymphocyte commitment and differentiation from hematopoietic stem cells
Jiang Zhu1,
Russell Garrett1,
Younghun Jung2,
Yi Zhang1,
Nacksung Kim3,
Jingcheng Wang2,
Gerard J. Joe1,
Elizabeth Hexner1,
Yongwon Choi1,3,
Russell S. Taichman2, and
Stephen G. Emerson1,3
1 Departments of Medicine, Pathology, and Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA;
2 Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI;
3 Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA
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 (OBs) support hematopoietic stem cell (HSC) proliferation and myeloid differentiation. We now find that purified primary murine OBs 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 to B cells requires their attachment to OBs 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 nonosteoblastic stromal cells (c-Kit ligand, IL-6, and IL-3) shifted the cultures toward myelopoiesis. Confirming the role of OBs 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 homolog of the avian bursa of Fabricius.
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