Study on the mechanism of prion protein accumulations in follicular dendritic cells.

克雅氏病（CDJ）、Gerstmann-Straussler综合征（GSS）和羊瘙痒症是传染性神经退行性疾病。提纯羊瘙痒病病原体的尝试导致了一种名为朊病毒蛋白（PrP）的糖蛋白的分离。PrP的蛋白酶抗性异构体PrPCJD或PrPSc被认为是痒病和DJD感染因子的主要成分。在中枢神经系统受累之前，该因子的复制和PrPSc的积累都发生在淋巴网状系统，特别是脾脏。滤泡树突状细胞（FDC）是淋巴组织中的主要抗原呈递细胞，是被CDJ试剂在小鼠中连续传代感染的小鼠的淋巴网状系统中PrPCJD的积聚部位。无论是通过脑内还是腹膜内途径接种，均在接种后30天内在脾脏中观察到PrPCJD在FDC中的蓄积，并且不依赖于试剂菌株。然而，在接种人CDJ或GSS材料的小鼠（第一代小鼠）中不会发生FDC中PrPCJD的累积，而在接种CJD试剂的小鼠中，一旦其适应小鼠，则总是发生。因此，这些现象可能表明在淋巴网状系统中的物种屏障的强烈表达。我们的数据表明，在淋巴网状系统中的物种屏障的进一步意义如下：SCID小鼠是唯一的菌株，其中PrPCJD没有积累在FDC接种后，小鼠适应的CJD菌株;此外，该CJD菌株通过腹腔内途径传播到SCID小鼠是不成功的，而通过脑内途径是成功的。这些数据表明，PrPCJD在FDC中的积累可能是腹膜内接种的CJD制剂侵入中枢神经系统的必要步骤。

Creutzfeldt-Jakob disease (CDJ), Gerstmann-Straussler syndrome (GSS) and scrapie are transmissible neurodegenerative diseases. Attempts to purify the scrapie agent have led to the descovery of a glycoprotein designated prion protein (PrP). The proteinase-resistant isoform of PrP named PrPCJD or PrPSc has been implicated as a main component of the infectious agent of scrapie and DJD.Both the replication of the agent and the accumulation of PrPSc occur in the lymphoreticular system, notably in the spleen, long gefore the involvement of the central nervous system. The follicular dendritic cell (FDC), a major antigen-presenting cell in the lymphoid tissue, is the site of accumulation of PrPCJD in the lymphoreticular system of mice infected by the CDJ agent passed serially in mice. The accumulation of PrPCJD in FDCs has been observed in the spleen within 30 days after inoculation of the agent whether via the intracerebral or the intraperitoneal route and does not depend on the agent strain. However, the ccumulation of PrPCJD in FDCs does not occur in mice inoculated with human CDJ or GSS materials (first-passage mice), whereas it always occurs in mice inoculated with the CJD agent once it has been adapted to the mouse. These phenomena may thus suggest an intense expression of the species barrier in the lymphoreticular system. Further significance of the species barrier in the lymphoreticular system might be suggested by our data as follows : the SCID mouse is the only strain in which PrPCJD did not accumulate in FDCs after inoculation of the mouse-adapted CJD strain ; in addition, transmission of this CJD strain to the SCID mouse via the intraperitoneal route was unsuccessful whereas that via the intracerebral route was successful. These data suggest the possibility that the accumulation of PrPCJD in FDCs is an essential step for the intraperitoneal- inoculated CJD agent to invade the central nervous system.