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Analysis of intramedullary extramedullary B lymphopoiesis

髓内髓外B淋巴细胞生成分析

基本信息

批准号：
13670318
负责人：
HAYASHI Shinichi
金额：
$ 2.24万
依托单位：
Tottori University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

Using three osteopetrotic mutant mouse strains, which carry reducing bone marrow formation, we have found their B lumphopoiesis lacks in rudimentary bone marrow cavities. The phylogenetical observation supports our finding, suggesting the presence of the relation between osteoclasts and B lymphopoiesis. To be clear the question, this study was performed.The results are shown as follows:1) In bone marrow B lymphopoiesis, Wnt-3a acts stromal cells, resulting in suppressing B lymphopoiesis. However, the factor does not affect osteoclastogenesis.2) Notch signaling is known to inhibit B lymphopoiesis. We assessed the effect of Notch signaling on osteoclastogenesis by using a recombinant ligand, Delta-1. The Notch signaling suppresses osteoclastogenesis directed to osteoclast precursors and through stromal cells, which support osteoclast development.3) Indicating the responsiveness to ligands for toll-like receptors and tumor necrosis factor-α, we demonstrated the presence of distinct osteoclast precursors maintained in each tissue including bone marrow, spleen, peritoneal cavity, and fetal liver.4) We developed the culture system of embryonic stem cells to induce the differentiation of ES cells to osteoclasts, endothelial cells, and osteobasts.Now, we have a model system to study in vitro bone marrow formation.We have already published the papers [1),2),and4)], and the manuscript for 3) has been submitted. Recently, based on our propose, candidate genes for regulating B lymphopoiesis in bone marrow are reported. We will make clear the mechanism of B lymphopoiesis, soon.

使用三种骨髓形成减少的骨硬化突变小鼠品系，我们发现它们的 B 肿块生成缺乏原始骨髓腔。系统发育观察支持我们的发现，表明破骨细胞和 B 淋巴细胞生成之间存在关系。为了明确这个问题，进行了本研究。结果如下：1)在骨髓B淋巴细胞生成中，Wnt-3a作用于基质细胞，导致B淋巴细胞生成受到抑制。然而，该因子不会影响破骨细胞生成。2) Notch 信号传导已知可抑制 B 淋巴细胞生成。我们通过使用重组配体 Delta-1 评估了 Notch 信号传导对破骨细胞生成的影响。 Notch 信号传导抑制针对破骨细胞前体并通过基质细胞的破骨细胞生成，从而支持破骨细胞的发育。3) 表明对 Toll 样受体和肿瘤坏死因子-α 配体的反应，我们证明了在包括骨髓、脾脏、腹膜腔和胎儿在内的每个组织中都存在不同的破骨细胞前体。 4）我们开发了胚胎干细胞培养系统，诱导ES细胞向破骨细胞、内皮细胞和成骨细胞分化。现在，我们有了一个研究体外骨髓形成的模型系统。我们已经发表了论文[1),2),和4)]，并且3）的手稿已经提交。最近，根据我们的提议，报道了调节骨髓中B淋巴细胞生成的候选基因。我们很快就会弄清楚B淋巴细胞生成的机制。