Unswitched immunoglobulin M response prolongs mouse survival in prion disease

Tayebi, M and Collinge, J and Hawke, S (2009) Unswitched immunoglobulin M response prolongs mouse survival in prion disease. JOURNAL OF GENERAL VIROLOGY, 90 (3). pp. 777-782.

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Abstract

Several studies have failed to demonstrate the presence of immune responses to infectious prions during the course of prion disease, reflecting the identical primary structure of normal and disease-associated isoforms and the widespread expression of the normal cellular form of prion protein, PrP<sup>c</sup>, leading to B- and/or T-cell tolerance of disease-associated isoforms and also possibly because antigen-presenting cells are unable to process the highly aggregated, detergent-insoluble, protease-resistant form, PrP<sup>Sc</sup>. Under certain circumstances, PrP<sup>Sc</sup> can be revealed to the immune system in immunogenic form, and it has been shown previously that anti-PrP antibodies can be induced to prions immunoadsorbed to Dynabeads using specific anti-PrP monoclonal antibodies, even in PrP-sufficient mice. This study demonstrated in a murine scrapie model that PrP-Dynabeads effectively stimulated the immune system to produce anti-PrP IgM antibodies over prolonged periods after repeated immunization. It was also shown that these immune responses prolonged incubation times in murine scrapie.

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