Analysis of intramedullary extramedullary B lymphopoiesis

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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.