Care Matthew A, Stephenson Sophie J, Barnes Nicholas A, Fan Im, Zougman Alexandre, El-Sherbiny Yasser M, Vital Edward M, Westhead David R, Tooze Reuben M, Doody Gina M
Section of Experimental Haematology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, United Kingdom; Bioinformatics Group, Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom;
Section of Experimental Haematology, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, United Kingdom;
J Immunol. 2016 Aug 15;197(4):1447-59. doi: 10.4049/jimmunol.1600624. Epub 2016 Jun 29.
Plasma cells (PCs) as effectors of humoral immunity produce Igs to match pathogenic insult. Emerging data suggest more diverse roles exist for PCs as regulators of immune and inflammatory responses via secretion of factors other than Igs. The extent to which such responses are preprogrammed in B-lineage cells or can be induced in PCs by the microenvironment is unknown. In this study, we dissect the impact of IFNs on the regulatory networks of human PCs. We show that core PC programs are unaffected, whereas PCs respond to IFNs with distinctive transcriptional responses. The IFN-stimulated gene 15 (ISG15) system emerges as a major transcriptional output induced in a sustained fashion by IFN-α in PCs and linked both to intracellular conjugation and ISG15 secretion. This leads to the identification of ISG15-secreting plasmablasts/PCs in patients with active systemic lupus erythematosus. Thus, ISG15-secreting PCs represent a distinct proinflammatory PC subset providing an Ig-independent mechanism of PC action in human autoimmunity.
浆细胞（PCs）作为体液免疫的效应细胞，产生免疫球蛋白（Igs）以应对病原体侵袭。新出现的数据表明，浆细胞作为免疫和炎症反应的调节因子，通过分泌免疫球蛋白以外的因子发挥着更多样化的作用。这些反应在B淋巴细胞系细胞中预先编程的程度，或者在浆细胞中由微环境诱导的程度尚不清楚。在本研究中，我们剖析了干扰素（IFNs）对人浆细胞调节网络的影响。我们发现，浆细胞的核心程序未受影响，而浆细胞对干扰素的反应具有独特的转录应答。干扰素刺激基因15（ISG15）系统是干扰素-α在浆细胞中持续诱导产生的主要转录产物，与细胞内缀合和ISG15分泌均有关联。这使得我们在活动性系统性红斑狼疮患者中鉴定出了分泌ISG15的浆母细胞/浆细胞。因此，可以分泌ISG15的浆细胞代表了一个独特的促炎浆细胞亚群，它在人类自身免疫中提供了一种不依赖免疫球蛋白的浆细胞作用机制。
