Osaki Yohei, Yokohama Akihiko, Saito Akio, Tahara Kenichi, Yanagisawa Kunio, Ogawa Yoshiyuki, Ishizaki Takuma, Mitsui Takeki, Koiso Hiromi, Takizawa Makiko, Uchiumi Hideki, Saitoh Takayuki, Handa Hiroshi, Murakami Hirokazu, Tsukamoto Norifumi, Nojima Yoshihisa
Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
PLoS One. 2013 Nov 29;8(11):e81722. doi: 10.1371/journal.pone.0081722. eCollection 2013.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy. Plasmacytoid DCs (pDCs), which are defined as lineage marker (Lin)(-)HLA-DR(+)CD56(-)CD123(+)CD11c(-) cells, are considered to be the normal counterpart of BPDCNs. However, BPDCN can be distinguished from pDCs by uniform expression of CD56. In this study, to identify a normal counterpart of BPDCN, we searched for a Lin(-)HLA-DR(+)CD56(+) population and focused on a minor subpopulation of Lin(-)DR(+)CD56(+)CD123(+)CD11c(-) cells that we designated as pDC-like cells (pDLCs). pDLC constituted 0.03% of peripheral blood mononuclear cells (PBMCs), and the pDLC/pDC ratio was higher in bone marrow cells than in PBMCs. pDLC clearly expressed BDCA2, BDCA4, and myeloid antigens, which are frequently expressed by BPDCN. pDLCs exhibited modest expression of Toll-like receptors and produced less interferon-α after CpG stimulation, but presented very low endocytic ability unlike mDCs. These functional differences were attributed to the expression profile of transcriptional factors. After in vitro culture with Flt3-ligand and GM-CSF, pDLCs expressed CD11c and BDCA1. These data suggested that pDLCs are a distinct subpopulation, with an immunophenotype similar to BPDCNs. Moreover, our results indicate that pDLCs might be immature DCs and might contribute to the immunophenotypical diversity of BPDCNs.
母细胞样浆细胞样树突状细胞肿瘤（BPDCN）是一种罕见的血液系统恶性肿瘤。浆细胞样树突状细胞（pDC）被定义为谱系标志物（Lin）（-）HLA-DR（+）CD56（-）CD123（+）CD11c（-）细胞，被认为是BPDCN的正常对应物。然而，BPDCN可通过CD56的均匀表达与pDC区分开来。在本研究中，为了确定BPDCN的正常对应物，我们寻找了Lin（-）HLA-DR（+）CD56（+）群体，并关注Lin（-）DR（+）CD56（+）CD123（+）CD11c（-）细胞的一个小亚群，我们将其命名为pDC样细胞（pDLC）。pDLC占外周血单个核细胞（PBMC）的0.03%，骨髓细胞中的pDLC/pDC比值高于PBMC。pDLC明显表达BDCA2、BDCA4和髓系抗原，这些抗原在BPDCN中经常表达。pDLCs表现出适度的Toll样受体表达，在CpG刺激后产生较少的干扰素-α，但与mDCs不同，其吞噬能力非常低。这些功能差异归因于转录因子的表达谱。在用Flt3配体和GM-CSF进行体外培养后，pDLCs表达CD11c和BDCA1。这些数据表明pDLCs是一个独特的亚群，其免疫表型与BPDCN相似。此外，我们的结果表明pDLCs可能是未成熟的DCs，可能有助于BPDCNs的免疫表型多样性。
