共刺激免疫原 LPS 诱导浸润移植人类肾脏的 B 细胞克隆。
The costimulatory immunogen LPS induces the B-Cell clones that infiltrate transplanted human kidneys.
机构信息
Departments of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
出版信息
Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):6036-41. doi: 10.1073/pnas.1202214109. Epub 2012 Apr 6.
Abstract
The mechanism of chronic rejection of transplanted human kidneys is unknown. An understanding of this process is important because, chronic rejection ultimately leads to loss of the kidney allograft in most transplants. One feature of chronic rejection is the infiltration of ectopic B-cell clusters that are clonal into the transplanted kidney. We now show that the antibodies produced by these B-cells react strongly with the core carbohydrate region of LPS. Since LPS is a costimulatory immunogen that can react with both the B-cell receptor (BCR) and the Toll-like receptor 4 (TLR4), these results suggest a mechanism for the selective pressure that leads to clonality of these B-cell clusters and opens the possibility that infection and the attendant exposure to LPS plays a role in the chronic rejection of human kidney transplants. If confirmed by clinical studies, these results suggest that treating patients with signs of chronic rejection with antibiotics may improve kidney allograft survival.
摘要
移植人体肾脏慢性排斥的机制尚不清楚。了解这一过程很重要，因为慢性排斥最终会导致大多数移植中的肾脏移植物丧失。慢性排斥的一个特征是异位 B 细胞簇的浸润，这些 B 细胞簇是克隆的。我们现在表明，这些 B 细胞产生的抗体与 LPS 的核心碳水化合物区域强烈反应。由于 LPS 是一种共刺激免疫原，可与 B 细胞受体 (BCR) 和 Toll 样受体 4 (TLR4) 反应，这些结果为导致这些 B 细胞簇克隆性的选择性压力提供了一种机制，并为感染和随之而来的 LPS 暴露在人类肾脏移植的慢性排斥中发挥作用提供了可能性。如果临床研究得到证实，这些结果表明，用抗生素治疗有慢性排斥迹象的患者可能会提高肾脏移植物的存活率。
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