Berggren Olof, Hagberg Niklas, Weber Gert, Alm Gunnar V, Rönnblom Lars, Eloranta Maija-Leena
Uppsala University, Uppsala, Sweden.
Arthritis Rheum. 2012 Oct;64(10):3409-19. doi: 10.1002/art.34599.
The type I interferon (IFN) system and B cells are activated in many autoimmune diseases, such as systemic lupus erythematosus (SLE). The IFNα produced by plasmacytoid dendritic cells (PDCs) stimulates several B cell functions, including autoantibody production. However, not much is known about how B cells influence PDC function. The aim of this study was to investigate the regulatory effect of B cells on IFNα production by PDCs.
PDCs and B cells isolated from peripheral blood mononuclear cells from healthy blood donors were stimulated with RNA-containing immune complexes (ICs) consisting of U1 small nuclear RNP and SLE IgG, herpes simplex virus, or oligonucleotide (ODN) 2216, alone or in cocultures. IFNα, several other cytokines, and PDC- or B cell-associated surface molecules were analyzed using immunoassays or flow cytometry.
B cells enhanced IFNα production by PDCs up to 47-fold, and the effect was most pronounced for PDCs stimulated with RNA-containing ICs. Anti-CD31 antibody reduced RNA-containing IC-induced IFNα production by 80% but had no effect on IFNα production when ODN 2216 was used as an inducer. Supernatants from ODN 2216-stimulated B cells promoted IFNα production by PDCs, while supernatants from RNA-containing IC-stimulated B cells did not.
Our results showed that a novel function of B cells is enhancement of type I IFN production by PDCs. Because B cells are activated by type I IFN, this PDC-B cell cross-talk might be of fundamental importance in the etiopathogenesis of SLE and contribute to long-term immune activation in SLE and other systemic rheumatic diseases.
在许多自身免疫性疾病中，如系统性红斑狼疮（SLE），I型干扰素（IFN）系统和B细胞会被激活。浆细胞样树突状细胞（pDC）产生的IFNα可刺激多种B细胞功能，包括自身抗体的产生。然而，关于B细胞如何影响pDC功能的了解并不多。本研究的目的是探讨B细胞对pDC产生IFNα的调节作用。
从健康献血者外周血单个核细胞中分离出的pDC和B细胞，单独或共培养，用含U1小核核糖核蛋白和SLE IgG的含RNA免疫复合物（IC）、单纯疱疹病毒或寡核苷酸（ODN）2216刺激。使用免疫测定或流式细胞术分析IFNα、其他几种细胞因子以及pDC或B细胞相关表面分子。
B细胞可将pDC产生的IFNα提高多达47倍，对于用含RNA的IC刺激的pDC，这种作用最为明显。抗CD31抗体使含RNA的IC诱导的IFNα产生减少80%，但当使用ODN 2216作为诱导剂时，对IFNα产生没有影响。ODN 2216刺激的B细胞的上清液促进pDC产生IFNα，而含RNA的IC刺激的B细胞的上清液则没有此作用。
我们的结果表明，B细胞的一个新功能是增强pDC产生I型干扰素。由于B细胞被I型干扰素激活，这种pDC - B细胞的相互作用可能在SLE的发病机制中具有根本重要性，并有助于SLE和其他系统性风湿性疾病的长期免疫激活。
