Distinct B-cell lineage commitment distinguishes adult bone marrow hematopoietic stem cells
Distinct B-cell lineage commitment distinguishes adult bone marrow hematopoietic stem cells
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DOI：
10.1073/pnas.1121632109
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发表时间：
2012-04-03
影响因子：
11.1
通讯作者：
Herzenberg, Leonore A.
中科院分区：
文献类型：
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作者：
Ghosn, Eliver Eid Bou;Yamamoto, Ryo;Herzenberg, Leonore A.
单个造血干细胞 (HSC) 是否会产生小鼠体内的所有 B 细胞亚群 [B-1a、B-1b、B-2 和边缘区 (MZ) B 细胞] 的问题已经讨论了很多年，但没有得到解决。这里的研究最终表明，从成人骨髓中分选出来的单个 HSC 并转移到接受致命辐射的受体中，明显会产生 B-2、MZ B 和 B-1b，但无法检测到重建 B-1a 细胞。这些发现将 B-2、MZ 和 B-1b 置于单个成人发育谱系中，并将 B-1a 置于源自成人中罕见或缺失的 HSC 的单独谱系中。我们讨论了关于其他 HSC 衍生的淋巴、髓系和红系谱系中已知的发育异质性的这些发现，以及 HSC 发育异质性如何符合我们几年前提出的免疫系统进化的分层模型。此外，对于当代医学很重要的是，我们考虑了 HSC 发育异质性对于选择用于人类移植的 HSC 来源可能产生的影响。
The question of whether a single hematopoietic stem cell (HSC) gives rise to all of the B-cell subsets [B-1a, B-1b, B-2, and marginal zone (MZ) B cells] in the mouse has been discussed for many years without resolution. Studies here finally demonstrate that individual HSCs sorted from adult bone marrow and transferred to lethally irradiated recipients clearly give rise to B-2, MZ B, and B-1b, but does not detectably reconstitute B-1a cells. These findings place B-2, MZ, and B-1b in a single adult developmental lineage and place B-1a in a separate lineage derived from HSCs that are rare or missing in adults. We discuss these findings with respect to known developmental heterogeneity in other HSC-derived lymphoid, myeloid, and erythroid lineages, and how HSC developmental heterogeneity conforms to the layered model of the evolution of the immune system that we proposed some years ago. In addition, of importance to contemporary medicine, we consider the implications that HSC developmental heterogeneity may have for selecting HSC sources for human transplantation.