Analysis of intramedullary extramedullary B lymphopoiesis

我们使用三种携带骨髓形成减少的骨硬化突变小鼠品系，发现它们的B造血在原始骨髓腔中缺乏。破骨细胞与B淋巴细胞生成之间存在着一定的关系。结果表明：1）在骨髓B淋巴细胞增殖中，Wnt-3a作用于基质细胞，抑制B淋巴细胞增殖。然而，该因子不影响破骨细胞生成。2）已知Notch信号传导抑制B淋巴细胞生成。我们通过使用重组配体Delta-1评估Notch信号传导对破骨细胞生成的影响。Notch信号传导抑制定向于破骨细胞前体并通过支持破骨细胞发育的基质细胞的破骨细胞生成。3）表明对toll样受体和肿瘤坏死因子-α的配体的反应性，我们证明了在包括骨髓、脾脏、腹膜腔、4）我们建立了胚胎干细胞的培养体系，诱导ES细胞向破骨细胞、内皮细胞和成骨细胞分化，目前已建立了体外研究骨髓形成的模型体系，已发表论文[1]，2）和4）]，3）的稿件已提交。近年来，基于我们的设想，骨髓B淋巴细胞增殖调控的候选基因陆续被报道。B淋巴细胞生成的机制有待进一步阐明。

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.