期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2001
卷号：98
期号：16
页码：9289-9294
DOI：10.1073/pnas.161055198
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：With the potential spread of bovine spongiform encephalopathy to people as a variant Creutzfeldt-Jakob disease (CJD), it becomes critical to identify cells in the periphery that carry infection. Initial work with scrapie agents suggested that B cells were central vectors for neuroinvasion. Subsequent studies indicated that B cells played an indirect role by promoting the development of follicular dendritic cells (FDCs) that accumulate abnormal prion protein (PrP). The mechanism for the role of FDCs, however, has not been clear. To further dissect potential B cell functions that contribute to neuroinvasion, we inoculated a CJD agent into mutant mice that (i) lacked B cells, (ii) had B cells unable to secrete Ig, or (iii) could secrete only IgM. Remarkably, all these mice developed disease with practically indistinguishable incubation times. The demonstration that neither immune complexes nor B cells were required for neuroinvasion from the periphery mandates a reanalysis of the accepted view of the essential role of B cells and FDC in these infections. Moreover, immune complexes were not required for the accumulation of pathologic PrP on the surface of FDCs, suggesting that PrP can bind to FDCs autonomously or by means of another factor. Wild-type mice had incubation times {approx}50 days less than all mutant mice at the same peripheral doses, indicating that an intact immune system may increase agent uptake and delivery, but this condition is not essential. Specifically, the evidence to date suggests that IgG may enhance pivotal agent interactions with migratory myeloid cells.
