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

Creutzfeldt-Jakob病（CDJ）， Gerstmann-Straussler综合征（GSS）和scrapie是传染性神经退行性疾病。在对痒病试剂进行纯化的过程中，发现了一种名为朊蛋白（PrP）的糖蛋白。PrP的蛋白酶抗性异构体PrPCJD或PrPSc已被认为是瘙痒病和ddd感染因子的主要成分。药物的复制和PrPSc的积累都发生在淋巴网状系统，特别是脾脏，早在中枢神经系统受累之前。滤泡树突状细胞（follicular dendritic cell， FDC）是淋巴组织中主要的抗原呈递细胞，是CDJ因子连续传递感染小鼠的淋巴网状系统中PrPCJD积累的部位。在接种疫苗后30天内，无论是通过脑内还是腹腔途径，均可在fdc中观察到PrPCJD在脾脏中的积累，并且与菌株无关。然而，PrPCJD在接种人CDJ或GSS材料的小鼠（首次传代小鼠）中不会在fdc中积累，而一旦CJD病原体适应小鼠，PrPCJD在接种CJD病原体的小鼠中总是会发生积累。因此，这些现象可能表明在淋巴网状系统中物种屏障的强烈表达。我们的数据可能进一步说明了在淋巴系统中物种屏障的意义：SCID小鼠是唯一在接种小鼠适应CJD菌株后PrPCJD没有在FDCs中积累的菌株；此外，该CJD毒株经腹腔途径向SCID小鼠传播不成功，而经脑内途径传播成功。这些数据提示，PrPCJD在FDCs中的积累可能是腹腔接种CJD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.