title: Identification of osteoblast stimulating factor 5 as a negative regulator in the B-lymphopoietic niche.
abstract: Recent studies have revealed the crucial role of the niche which supports B-lymphocyte differentiation from hematopoietic stem cells. In this study, we aimed to identify a novel regulator of B lymphopoiesis secreted in the specific niche using the signal sequence trap method. Among the identified proteins from MS5 stromal cells, expression of pleiotrophin, placental proliferin 2, and osteoblast stimulating factor 5 (OSF-5) was dominantly high in several stromal cell lines. We found that OSF-5 suppressed early B lymphopoiesis in transgenic mice producing the target protein. The number of pre-B and immature B cells was reduced by more than half compared with control in the transgenic mice. In vitro studies showed that a secreted variant of OSF-5 inhibited the proliferation and colony formation of pre-B cells, whereas cell-intrinsic form had no influence on B lymphopoiesis. The main components of the B-lymphopoietic niche, osteoblasts in mice and mesenchymal cells in humans, are primary producers of OSF-5. These results define a novel mechanism of B lymphopoiesis in bone marrow. In the specific niche, B-lymphocyte differentiation is fine-tuned by negative regulators as well as supportive factors.
authors.affiliation: Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Fujita
authors.affiliation: Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Ichii
authors.affiliation: Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Maeda
authors.affiliation: Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Saitoh
authors.affiliation: Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yokota
authors.affiliation: Nephrology Research Labs, Nephrology Research & Development Unit, Research & Development Division, Kyowa Hakko Kirin, Tokyo, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Yamawaki
authors.affiliation: Production Division, Bio Process Research and Development Labs, Kyowa Hakko Kirin, Gunma, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kakitani
authors.affiliation: Innovative Technology Labs, Research Functions Unit, Research & Development Division, Kyowa Hakko Kirin, Tokyo, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Tomizuka
authors.affiliation: Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan. Electronic address: oritani@bldon.med.osaka-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Oritani
authors.affiliation: Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Kanakura
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D038041:Lymphopoiesis / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000378:metabolism*; D055153:Stem Cell Niche / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; C066845:pleiotrophin