High frequency of autoantibody‐secreting cells and long‐lived plasma cells within inflamed kidneys of NZB/W F1 lupus mice
High frequency of autoantibody‐secreting cells and long‐lived plasma cells within inflamed kidneys of NZB/W F1 lupus mice
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DOI：
10.1002/eji.201041315
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发表时间：
2011-07
影响因子：
5.4
通讯作者：
Charlotte Starke;S. Frey;U. Wellmann;V. Urbonaviciute;M. Herrmann;K. Amann;G. Schett;T. Winkler;R. Voll
中科院分区：
文献类型：
--
作者：
Charlotte Starke;S. Frey;U. Wellmann;V. Urbonaviciute;M. Herrmann;K. Amann;G. Schett;T. Winkler;R. Voll
双链 (ds) DNA 自身抗体是系统性红斑狼疮 (SLE) 的血清学标志，可能在狼疮性肾炎的发病机制中发挥重要作用。自身反应性抗体可能部分由长寿浆细胞（PC）产生，这些浆细胞主要存在于骨髓和脾脏中。与短寿命 PC 相比，长寿命 PC 对治疗具有极强的抵抗力，并且可能维持难治性病程。最近，在新西兰黑/白 (NZB/W) F1 狼疮小鼠以及 SLE 患者发炎的肾脏中发现了抗体分泌细胞。为了分析 NZB/W F1 小鼠肾病肾脏中产生 IgG 的细胞的寿命，我们进行了体内 BrdU 标记。我们发现长寿命肾 PC 的出现频率高于短寿命肾 PC，这表明长寿命 PC 的生存空间也存在于发炎的肾脏内。使用 ELISPOT 检测，我们发现平均 31% 的肾脏 IgG 生成细胞与 dsDNA 发生反应，24% 与核仁素发生反应。此外，与脾脏和骨髓中的相比，肾脏中对自身抗原 dsDNA 和核仁素具有特异性的 IgG 分泌细胞的频率更高。
Autoantibodies to double‐stranded (ds) DNA represent a serological hallmark of systemic lupus erythematosus (SLE) and may critically contribute to the pathogenesis of lupus nephritis. Self‐reactive antibodies might be partially produced by long‐lived plasma cells (PCs), which mainly reside within the bone marrow and spleen. In contrast to short‐lived PCs, long‐lived PCs are extremely resistant to therapy and may sustain refractory disease courses. Recently, antibody‐secreting cells were found within the inflamed kidneys of New Zealand black/white (NZB/W) F1 lupus mice as well as of patients with SLE. To analyze the longevity of the IgG‐producing cells present in nephritic kidneys of NZB/W F1 mice we performed in vivo BrdU‐labeling. We identified a higher frequency of long‐lived than short‐lived renal PCs, indicating that survival niches for long‐lived PCs also exist within inflamed kidneys. Using ELISPOT assays, we found that on average 31% of renal IgG‐producing cells reacted with dsDNA and 24% with nucleolin. Moreover, the frequencies of IgG‐secreting cells specific for the autoantigens dsDNA and nucleolin were higher in the kidneys compared with those in the spleen and bone marrow.