Kamogawa-Schifter Yumiko, Ohkawa Jun, Namiki Sahori, Arai Naoko, Arai Ken-Ichi, Liu Yongjun
Department of Immunobiology, Ginkgo Biomedical Research Institute, 4-7-4-8F Shirokanedai, Minato-ku, Tokyo, 108-0071 Japan.
Blood. 2005 Apr 1;105(7):2787-92. doi: 10.1182/blood-2004-09-3388. Epub 2004 Dec 14.
Plasmacytoid dendritic cells (pDCs) play an important primary role for antiviral innate immunity by rapidly producing large amounts of type 1 interferon (IFN) upon viral infection. To study pDC biology, we generated a monoclonal antibody, termed 2E6, that recognizes pDCs. Molecular cloning of a cDNA encoding the 2E6 antigen revealed that it is a type II C-type lectin, Ly49Q, that consists of 247 amino acids with high homology to the natural killer (NK) receptor family Ly49, with an immunoreceptor tyrosine-based inhibitory motif in the cytoplasmic domain. Ly49Q is expressed on pDCs but not on NK cells or myeloid dendritic cells. B220+, CD11c+, CD11b- pDCs in bone marrow were divided into Ly49Q+ and Ly49Q- subsets. While both subsets produced IFN-alpha upon cytosine-phosphate-guanosine (CpG) and herpes simplex virus stimulation, Ly49Q- pDCs responded poorly to influenza virus. In addition, Ly49Q- pDCs produced inflammatory cytokines such as interleukin 6 (IL-6), IL-12, and tumor necrosis factor alpha (TNF-alpha) upon stimulation at lower levels than those produced by Ly49Q+ pDCs. In contrast to bone marrow, Ly49Q+ pDCs were only found in peripheral blood, lymph nodes, and spleen. These results indicate that Ly49Q is a specific marker for peripheral pDCs and that expression of Ly49Q defines 2 subsets of pDCs in bone marrow.
浆细胞样树突状细胞(pDCs)在抗病毒固有免疫中发挥重要的主要作用,在病毒感染后能迅速产生大量1型干扰素(IFN)。为了研究pDC生物学特性,我们制备了一种识别pDCs的单克隆抗体,命名为2E6。编码2E6抗原的cDNA分子克隆显示,它是一种II型C型凝集素,即Ly49Q,由247个氨基酸组成,与自然杀伤(NK)受体家族Ly49具有高度同源性,其胞质结构域含有基于免疫受体酪氨酸的抑制基序。Ly49Q在pDCs上表达,但在NK细胞或髓样树突状细胞上不表达。骨髓中B220+、CD11c+、CD11b-的pDCs可分为Ly49Q+和Ly49Q-亚群。虽然两个亚群在受到胞嘧啶-磷酸-鸟嘌呤(CpG)和单纯疱疹病毒刺激时都能产生IFN-α,但Ly49Q- pDCs对流感病毒的反应较差。此外,Ly49Q- pDCs在受到刺激时产生的炎性细胞因子如白细胞介素6(IL-6)、IL-12和肿瘤坏死因子α(TNF-α)的水平低于Ly49Q+ pDCs产生的水平。与骨髓不同,Ly49Q+ pDCs仅在外周血、淋巴结和脾脏中发现。这些结果表明,Ly49Q是外周pDCs的特异性标志物,Ly49Q的表达定义了骨髓中pDCs的两个亚群。