Earliest hematopoietic progenitors at embryonic day 9 preferentially generate B-1 B cells rather than follicular B or marginal zone B cells

Earliest hematopoietic progenitors at embryonic day 9 preferentially generate B-1 B cells rather than follicular B or marginal zone B cells
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DOI:
10.1016/j.bbrc.2013.06.073
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发表时间:
2013-07-26
影响因子:
3.1
通讯作者:
Yamane, Toshiyuki
Yamane, Toshiyuki
中科院分区:
生物学4区
文献类型:
--
作者:
Ito, Chie;Yamazaki, Hidetoshi;Yamane, Toshiyuki

文献摘要

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早在小鼠胚胎第 9 天 (E9),可移植造血干细胞 (HSC) 出现在 El 1 之前,就可以观察到造血系统的淋巴潜能。然而,目前尚不清楚哪个细胞部分负责最初的淋巴细胞生成波以及这些最早的淋巴细胞是否对成体淋巴系统做出任何贡献。我们之前在E9分离出具有CD45(+)c-Kit(+)AA4.1(+)表型的最早的血淋巴祖细胞。在这项研究中,详细检查了 E9 血淋巴祖细胞向 B 细胞亚群的分化能力。在培养中,E9造血淋巴祖细胞产生B220(-/低)B细胞祖细胞,与成人BM c-Kit(+)Sca-1(+)Lin(-)细胞形成鲜明对比。体内移植后,源自E9血淋巴祖细胞的B细胞祖细胞优先分化为B-1 B淋巴细胞亚群,而分化为B-2 B淋巴细胞亚群[滤泡B(FoB)、边缘区B(MZB)细胞]的效率低下。值得注意的是,即使成年小鼠被用作受体,这些供体 B 淋巴细胞也会永久地在宿主小鼠体内重新繁殖。这些结果表明,在真正的 HSC 出现之前,由初始造血波产生的 B 细胞祖细胞可能是至少 B-1 B 淋巴细胞亚群的永久来源。 (C) 2013 Elsevier Inc. 保留所有权利。
The lymphoid potential of the hematopoietic system is observed as early as embryonic day 9 (E9) before transplantable hematopoietic stem cells (HSCs) appear at El 1 in mice. However, it is largely unknown as to which cell fraction is responsible for the initial wave of lymphopoiesis and whether these earliest lymphocytes make any contributions to the adult lymphoid system. We previously isolated the earliest hematolymphoid progenitors at E9 that had CD45(+)c-Kit(+)AA4.1(+) phenotypes. In this study, the differentiation potency into B cell subsets of the E9 hematolymphoid progenitors was examined in detail. In culture, E9 hematolymphoid progenitors produced B220(-/low) B cell progenitors in striking contrast to adult BM c-Kit(+)Sca-l(+)Lin(-) cells. Upon in vivo transplantation, B cell progenitors derived from E9 hematolymphoid progenitors preferentially differentiated into the B-1 B lymphocyte subset, whereas their differentiation into B-2 B lymphocyte subsets [follicular B (FoB), marginal zone B (MZB) cells] was inefficient. Of note, these donor B lymphocytes permanently repopulated in host mice, even if adult mice were used as recipients. These results suggest that B cell progenitors produced from an initial wave of definitive hematopoiesis before authentic HSCs appear could be a permanent source for, at least, the B-1 B lymphocyte subset. (C) 2013 Elsevier Inc. All rights reserved.