Klein M A, Frigg R, Raeber A J, Flechsig E, Hegyi I, Zinkernagel R M, Weissmann C, Aguzzi A
Institute of Neuropathology, University of Zürich, Switzerland.
Nat Med. 1998 Dec;4(12):1429-33. doi: 10.1038/4022.
Prion diseases are typically initiated by infection of peripheral sites, as in the case of bovine spongiform encephalopathy, new variant Creutzfeldt-Jakob disease, kuru and most cases of iatrogenic Creutzfeldt-Jakob disease. In mouse scrapie, prion infectivity accumulates in lymphoid organs, and the absence of mature B lymphocytes prevents peripherally administered prions from inducing central nervous system disease. We have now assessed whether expression of the cellular prion protein, PrPc, is required for B lymphocytes to mediate neuroinvasion. We found that repopulation of SCID and Rag-1(-/-) mice with fetal liver cells from either PrP-expressing or PrP-deficient mice and from T-cell deficient mice, but not from B-cell deficient mice, is equally efficient in restoring neuroinvasion after intraperitoneal inoculation of scrapie prions. These results indicate that cells whose maturation depends on B cells or their products, such as follicular dendritic cells, may enhance neuroinvasion. Alternatively, B cells may transport prions to the nervous system by a PrP-independent mechanism.
朊病毒疾病通常由外周部位感染引发，如牛海绵状脑病、新型变异型克雅氏病、库鲁病以及大多数医源性克雅氏病病例。在小鼠瘙痒病中，朊病毒感染性在淋巴器官中积累，而成熟B淋巴细胞的缺失可阻止经外周给予的朊病毒诱发中枢神经系统疾病。我们现在评估了细胞朊蛋白PrPc的表达对于B淋巴细胞介导神经侵袭是否必需。我们发现，用来自表达PrP或缺乏PrP的小鼠以及T细胞缺陷小鼠（而非B细胞缺陷小鼠）的胎肝细胞重新填充SCID和Rag-1(-/-)小鼠，在腹腔接种瘙痒病朊病毒后恢复神经侵袭的效率相同。这些结果表明，其成熟依赖于B细胞或其产物的细胞，如滤泡树突状细胞，可能会增强神经侵袭。或者，B细胞可能通过一种不依赖PrP的机制将朊病毒转运至神经系统。
