Identification of osteoblast stimulating factor 5 as a negative regulator in the B-lymphopoietic niche
| Autor: | Natsuko Fujita, Michiko Ichii, Kengo Yamawaki, Yuzuru Kanakura, Tetsuo Maeda, Makoto Kakitani, Kazuma Tomizuka, Kenji Oritani, Norimitsu Saitoh, Takafumi Yokota |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Cancer Research Stromal cell Transgene Mice Transgenic Biology Pleiotrophin Mice Genetics medicine Animals Humans Stem Cell Niche Molecular Biology Cell Proliferation Lymphopoiesis Precursor Cells B-Lymphoid Mesenchymal stem cell Osteoblast Cell Differentiation Cell Biology Hematology Cell biology Haematopoiesis medicine.anatomical_structure Immunology Cytokines Female Bone marrow Stem cell Stromal Cells Carrier Proteins |
| Zdroj: | Experimental hematology. 43(11) |
| ISSN: | 1873-2399 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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