PrP expression in B lymphocytes is not required for prion neuroinvasion
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Published on: November 20, 2010
M A Klein1, R Frigg, A J Raeber
1Institute of Neuropathology, University of Zürich, Switzerland.
Abstract:
Prion diseases are typically initiated by infection of peripheral sites, as in the case of bovine spongiform encephalopathy, new variant Creutzfeldt-Jakob disease, kuru and most cases of iatrogenic Creutzfeldt-Jakob disease. In mouse scrapie, prion infectivity accumulates in lymphoid organs, and the absence of mature B lymphocytes prevents peripherally administered prions from inducing central nervous system disease. We have now assessed whether expression of the cellular prion protein, PrPc, is required for B lymphocytes to mediate neuroinvasion. We found that repopulation of SCID and Rag-1(-/-) mice with fetal liver cells from either PrP-expressing or PrP-deficient mice and from T-cell deficient mice, but not from B-cell deficient mice, is equally efficient in restoring neuroinvasion after intraperitoneal inoculation of scrapie prions. These results indicate that cells whose maturation depends on B cells or their products, such as follicular dendritic cells, may enhance neuroinvasion. Alternatively, B cells may transport prions to the nervous system by a PrP-independent mechanism.
Insights
B cells are not essential for prion diseases to reach the brain. However, B cell-dependent cells like follicular dendritic cells may enhance prion neuroinvasion, or B cells might transport prions independently of PrP.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Prion diseases often begin with peripheral infections, affecting lymphoid organs.
- Mature B lymphocytes are crucial for peripheral prions to cause central nervous system (CNS) disease in mice.
Purpose of the Study:
- To investigate if the cellular prion protein (PrPc) expression is necessary for B lymphocytes to mediate neuroinvasion.
- To understand the role of B cells and PrPc in prion transport to the CNS.
Main Methods:
- Repopulation of severe combined immunodeficient (SCID) and Rag-1 knockout mice with fetal liver cells.
- Utilized fetal liver cells from PrP-expressing, PrP-deficient, T-cell deficient, and B-cell deficient mice.
- Assessed neuroinvasion following intraperitoneal inoculation with scrapie prions.
Main Results:
- Repopulation with PrP-expressing or PrP-deficient cells, and T-cell deficient cells, efficiently restored neuroinvasion.
- Repopulation with B-cell deficient cells did not restore neuroinvasion.
- These findings suggest B cells are not essential for neuroinvasion.
Conclusions:
- B cells are not required for prion neuroinvasion.
- Cells dependent on B cells, like follicular dendritic cells, may enhance neuroinvasion.
- B cells might facilitate prion transport to the CNS via a PrP-independent pathway.
