INSERM U976, Université de Paris, École Pratique des Hautes Études/PSL Research University, Institut de Recherche Saint Louis, Paris, France.
INSERM U976, Université de Paris, École Pratique des Hautes Études/PSL Research University, Institut de Recherche Saint Louis, Paris, France; Laboratoire Cognitions Humaine et Artificielle (CHArt) EA 4004 FED 4246, École Pratique des Hautes Études/PSL Research University, Paris, France.
Cell Rep. 2023 Jun 27;42(6):112618. doi: 10.1016/j.celrep.2023.112618. Epub 2023 Jun 8.
Changes in lymphocyte production patterns occurring across human ontogeny remain poorly defined. In this study, we demonstrate that human lymphopoiesis is supported by three waves of embryonic, fetal, and postnatal multi-lymphoid progenitors (MLPs) differing in CD7 and CD10 expression and their output of CD127 early lymphoid progenitors (ELPs). In addition, our results reveal that, like the fetal-to-adult switch in erythropoiesis, transition to postnatal life coincides with a shift from multilineage to B lineage-biased lymphopoiesis and an increase in production of CD127 ELPs, which persists until puberty. A further developmental transition is observed in elderly individuals whereby B cell differentiation bypasses the CD127 compartment and branches directly from CD10 MLPs. Functional analyses indicate that these changes are determined at the level of hematopoietic stem cells. These findings provide insights for understanding identity and function of human MLPs and the establishment and maintenance of adaptative immunity.
人类个体发育过程中淋巴细胞生成模式的变化仍未得到明确界定。在这项研究中，我们证明人类淋巴样发生由三个波的胚胎、胎儿和出生后多淋巴样祖细胞（MLP）支持，这些祖细胞在 CD7 和 CD10 的表达及其 CD127 早期淋巴样祖细胞（ELP）的输出上存在差异。此外，我们的结果表明，与红系造血从胎儿到成人的转变一样，向出生后生命的过渡伴随着从多谱系偏向性向 B 谱系偏向性淋巴样发生的转变，以及 CD127 ELP 产量的增加，这种情况一直持续到青春期。在老年人中还观察到另一个发育性转变，即 B 细胞分化绕过 CD127 区室，直接从 CD10 MLP 分支。功能分析表明，这些变化是在造血干细胞水平上决定的。这些发现为理解人类 MLP 的特性和功能以及适应性免疫的建立和维持提供了新的思路。
