title: Osteoblasts support B-lymphocyte commitment and differentiation from hematopoietic stem cells.
abstract: 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 Col2.3Delta-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.
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania School of Medicine, 3600 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.forename: Russell
authors.initials: R
authors.lastname: Garrett
authors.forename: Younghun
authors.initials: Y
authors.lastname: Jung
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Nacksung
authors.initials: N
authors.lastname: Kim
authors.forename: Jingcheng
authors.initials: J
authors.lastname: Wang
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Joe
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hexner
authors.forename: Yongwon
authors.initials: Y
authors.lastname: Choi
authors.forename: Russell S
authors.initials: RS
authors.lastname: Taichman
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Emerson
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D001717:Birds / Q000378:metabolism; D002060:Bursa of Fabricius / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D038041:Lymphopoiesis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D051381:Rats
chemical_list: D000943:Antigens, Differentiation; D016207:Cytokines