Abbey Janice L, Karsunky Holger, Serwold Thomas, Papathanasiou Peter, Weissman Irving L, O'Neill Helen C
Research School of Biology, Australian National University, Canberra, ACT, Australia.
Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
J Cell Mol Med. 2015 Aug;19(8):1956-64. doi: 10.1111/jcmm.12572. Epub 2015 Mar 6.
Germline transcription has been described for both immunoglobulin and T-cell receptor (TCR) genes, raising questions of their functional significance during haematopoiesis. Previously, an immature murine T-cell line was shown to bind antibody to TCR-Vβ8.2 in absence of anti-Cβ antibody binding, and an equivalent cell subset was also identified in the mesenteric lymph node. Here, we investigate whether germline transcription and cell surface Vβ8.2 expression could therefore represent a potential marker of T-cell progenitors. Cells with the TCR phenotype of Vβ8.2(+) Cβ(-) are found in several lymphoid sites, and among the lineage-negative (Lin(-)) fraction of hematopoietic progenitors in bone marrow (BM). Cell surface marker analysis of these cells identified subsets reflecting common lymphoid progenitors, common myeloid progenitors and multipotential progenitors. To assess whether the Lin(-) Vβ8.2(+) Cβ(-) BM subset contains hematopoietic progenitors, cells were sorted and adoptively transferred into sub-lethally irradiated recipients. No T-cell or myeloid progeny were detected following introduction of cells via the intrathymic or intravenous routes. However, B-cell development was detected in spleen. This pattern of restricted in vivo reconstitution disputes Lin(-) Vβ8.2(+) Cβ(-) BM cells as committed T-cell progenitors, but raises the possibility of progenitors with potential for B-cell development.
免疫球蛋白和T细胞受体(TCR)基因均已被描述为种系转录,这引发了关于它们在造血过程中的功能意义的问题。此前,已证明一种未成熟的鼠T细胞系在不存在抗Cβ抗体结合的情况下能与抗TCR-Vβ8.2抗体结合,并且在肠系膜淋巴结中也鉴定出了等效的细胞亚群。在此,我们研究种系转录和细胞表面Vβ8.2表达是否因此可能代表T细胞祖细胞的潜在标志物。具有Vβ8.2(+) Cβ(-) TCR表型的细胞存在于多个淋巴部位,以及骨髓(BM)中造血祖细胞的谱系阴性(Lin(-))部分中。对这些细胞的细胞表面标志物分析确定了反映常见淋巴祖细胞、常见髓系祖细胞和多能祖细胞的亚群。为了评估Lin(-) Vβ8.2(+) Cβ(-) BM亚群是否包含造血祖细胞,对细胞进行分选并过继转移到亚致死剂量照射的受体中。通过胸腺内或静脉内途径引入细胞后,未检测到T细胞或髓系后代。然而,在脾脏中检测到了B细胞发育。这种体内重建受限的模式对Lin(-) Vβ8.2(+) Cβ(-) BM细胞作为定向T细胞祖细胞提出了质疑,但增加了具有B细胞发育潜力的祖细胞的可能性。