Neuroinvasion by a Creutzfeldt–Jakob disease agent in the absence of B cells and follicular dendritic cells
AUTOR(ES)
Shlomchik, Mark J.
FONTE
The National Academy of Sciences
RESUMO
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 ≈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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=55413Documentos Relacionados
- Follicular Dendritic Cells and Dissemination of Creutzfeldt-Jakob Disease
- Abnormal isoform of prion protein accumulates in follicular dendritic cells in mice with Creutzfeldt-Jakob disease.
- Physical properties of the Creutzfeldt-Jakob disease agent.
- Transmissible agent in the amyotrophic form of Creutzfeldt-Jakob disease.
- Creutzfeldt-Jakob disease, 1988.