Tagaya H, Kunisada T, Yamazaki H, Yamane T, Tokuhisa T, Wagner E F, Sudo T, Shultz L D, Hayashi S I
Department of Immunology, School of Life Science, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan.
Blood. 2000 Jun 1;95(11):3363-70.
Adult bone marrow is a major site for hematopoiesis, and reduction of the bone marrow cavity induces hematopoiesis in extramarrow tissues. To investigate the rudimentary intramarrow and the compensatory extramarrow hematopoiesis, particularly B lymphopoiesis, we used 3 osteopetrotic mouse strains [op/op, mi/mi, and Fos (-/-)], which are severely deficient in functional osteoclasts and therefore form inadequate bone marrow cavities. We found that bone marrow in these osteopetrotic mice supports myelopoiesis but not B lymphopoiesis, although cells that have the potential to differentiate into B lineage cells are present in the bone marrow. Although B lymphopoiesis normally occurs both in the spleen and liver of newborn mice, compensatory B lymphopoiesis in adult op/op and mi/mi mice is observed only in the liver, while myelopoiesis is enhanced in both organs. Interestingly, mice lacking the Fos proto-oncogene exhibit B lymphopoiesis in the spleen as well as liver. The amounts of expression of steel factor, Flt3/Flk-2 ligand, and interleukin-7 in the bone marrow, spleen, or liver were not significantly affected in these osteopetrotic mutants. These findings suggest that the volume of the bone marrow cavity regulates B lymphopoiesis without affecting the production of certain hematopoietic growth factors. The splenic microenvironments that support both myelopoiesis and B lymphopoiesis in the neonatal stage are lost in adults and are not reactivated even in the osteopetrotic adults unless the Fos gene is disrupted.
成年骨髓是造血的主要部位，骨髓腔的缩小会诱导髓外组织造血。为了研究原始的骨髓内造血和代偿性髓外造血，特别是B淋巴细胞生成，我们使用了3种骨石化小鼠品系[op/op、mi/mi和Fos(-/-)]，这些品系功能性破骨细胞严重缺乏，因此形成的骨髓腔不足。我们发现，这些骨石化小鼠的骨髓支持髓细胞生成，但不支持B淋巴细胞生成，尽管骨髓中存在有分化为B系细胞潜力的细胞。虽然B淋巴细胞生成通常发生在新生小鼠的脾脏和肝脏中，但成年op/op和mi/mi小鼠的代偿性B淋巴细胞生成仅在肝脏中观察到，而两个器官中的髓细胞生成均增强。有趣的是，缺乏Fos原癌基因的小鼠在脾脏和肝脏中均表现出B淋巴细胞生成。在这些骨石化突变体中，骨髓、脾脏或肝脏中钢因子、Flt3/Flk-2配体和白细胞介素-7的表达量没有受到显著影响。这些发现表明，骨髓腔的容积调节B淋巴细胞生成，而不影响某些造血生长因子的产生。在新生儿期支持髓细胞生成和B淋巴细胞生成的脾脏微环境在成年后丧失，即使在骨石化成年小鼠中也不会重新激活，除非Fos基因被破坏。
