Kikuchi Kazu, Kondo Motonari
Department of Immunology, Duke University Medical Center, Research Drive, Durham, NC 27710, USA.
Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17852-7. doi: 10.1073/pnas.0603368103. Epub 2006 Nov 7.
Hematopoiesis originated by hematopoietic stem cells (HSCs) is distinguishable between fetal and adult mice. However, it is not clear whether the altered mode of differentiation is due to the change of properties of HSCs or different microenvironments in fetuses and adults. Here we show that fetal HSCs are fully capable of giving rise to all classes of B cells in the adult microenvironment. HSCs that are derived from fetal liver but not adult bone marrow (BM) of IL-7 receptor alpha chain (IL-7Ralpha)-deficient mice can also differentiate into B cells, suggesting that both IL-7 and thymic stromal-derived lymphopoietin (TSLP) are dispensable for fetal B cell development, because IL-7Ralpha is commonly used as a subunit of functional receptor complexes for IL-7 and TSLP. Similar IL-7/TSLP independent B cell potential is maintained by BM HSCs until 1 week after birth. In contrast, BM HSCs in mice older than 2 weeks of age absolutely requires IL-7Ralpha for B lymphopoiesis. These results demonstrate that fetal HSCs acquired adult characteristics between 1 and 2 weeks after birth in mouse BM.
造血干细胞(HSC)产生的造血作用在胎儿和成年小鼠之间存在差异。然而,尚不清楚分化模式的改变是由于造血干细胞特性的变化还是胎儿和成年个体中不同的微环境所致。在此我们表明,胎儿造血干细胞完全有能力在成年微环境中产生所有类型的B细胞。源自白细胞介素7受体α链(IL-7Rα)缺陷小鼠的胎儿肝脏而非成年骨髓(BM)的造血干细胞也能分化为B细胞,这表明白细胞介素7(IL-7)和胸腺基质衍生的淋巴细胞生成素(TSLP)对于胎儿B细胞发育都是可有可无的,因为IL-7Rα通常用作IL-7和TSLP功能性受体复合物的一个亚基。骨髓造血干细胞在出生后1周内都保持类似的不依赖IL-7/TSLP的B细胞生成潜能。相比之下,2周龄以上小鼠的骨髓造血干细胞进行B淋巴细胞生成绝对需要IL-7Rα。这些结果表明,胎儿造血干细胞在出生后1至2周内在小鼠骨髓中获得了成年特征。