Center for Autoimmunity and Musculoskeletal Diseases, Feinstein Institute for Medical Research, Manhasset, New York, NY 11030, USA.
Eur J Immunol. 2011 Mar;41(3):588-91. doi: 10.1002/eji.201041354. Epub 2011 Feb 10.
Plasma cells can be classified as long- or short-lived. The lifespan of a plasma cell largely depends on whether it arises from a germinal center or an extrafollicular locus and most importantly whether it can find a survival niche in the spleen or BM. In systemic lupus erythematosus (SLE) patients, long-lived plasma cells are believed to be responsible for the production of anti-RNA and anti-cardiolipin antibodies, whereas short-lived plasma cells, which are more susceptible to anti-proliferation therapies, are the main producers of anti-DNA antibodies. A previous study showed that transient overexpression of interferon-α (IFN-α), a cytokine that plays a pathogenic role in SLE, accelerates disease onset in lupus-prone NZB/W mice. In this issue of the European Journal of Immunology, the same group report that IFN-α induces large numbers of short-lived plasma cells, accompanied by high titers of anti-dsDNA antibodies in NZB/W, but not BALB/c, mice. Our commentary discusses this interesting observation in the context of the previous data regarding plasma cell differentiation and conveys our view about the clinical implications with respect to therapies that target plasma cells in SLE patients.
浆细胞可以分为长寿命和短寿命。浆细胞的寿命在很大程度上取决于它是来自生发中心还是滤泡外部位,最重要的是它是否能在脾脏或骨髓中找到生存龛位。在系统性红斑狼疮(SLE)患者中,长寿命浆细胞被认为是产生抗 RNA 和抗心磷脂抗体的原因,而短寿命浆细胞更容易受到抗增殖治疗的影响,是产生抗 DNA 抗体的主要产生者。先前的一项研究表明,细胞因子干扰素-α(IFN-α)的短暂过表达会加速狼疮易感 NZB/W 小鼠的疾病发作,IFN-α 在 SLE 中起致病作用。在本期《欧洲免疫学杂志》中,同一研究小组报告称,IFN-α 在 NZB/W 小鼠中诱导大量短寿命浆细胞,同时伴有高滴度的抗 dsDNA 抗体,但在 BALB/c 小鼠中则没有。我们的评论在以前关于浆细胞分化的研究数据的背景下讨论了这一有趣的观察结果,并就针对 SLE 患者浆细胞的治疗的临床意义表达了我们的观点。