Abstract
Prion diseases are a unique, infectious, neurodegenerative disorders that can affect animals and humans. Data from mouse transmissions show that efficient infection of the host after intravenous (IV) prion exposure is dependent upon the early accumulation and amplification of the prions on stromal follicular dendritic cells (FDC) in the B cell follicles. How infectious prions are initially conveyed from the blood-stream to the FDC in the spleen is uncertain. Addressing this issue is important as susceptibility to peripheral prion infections can be reduced by treatments that prevent the early accumulation of prions upon FDC. The marginal zone (MZ) in the spleen contains specialized subsets of B cells and macrophages that are positioned to continuously monitor the blood-stream and remove pathogens, toxins and apoptotic cells. The continual shuttling of MZ B cells between the MZ and the B-cell follicle enables them to efficiently capture and deliver blood-borne antigens and antigen-containing immune complexes to splenic FDC. We tested the hypothesis that MZ B cells also play a role in the initial shuttling of prions from the blood-stream to FDC. MZ B cells were temporarily depleted from the MZ by antibody-mediated blocking of integrin function. We show that depletion of MZ B cells around the time of IV prion exposure did not affect the early accumulation of blood-borne prions upon splenic FDC or reduce susceptibility to IV prion infection. In conclusion, our data suggest that the initial delivery of blood-borne prions to FDC in the spleen occurs independently of MZ B cells.
Highlights
Prion diseases are a unique, infectious, neurodegenerative disorders that can affect animals and humans
Cells express the integrins LFA-1 and α4β1 highly and this enables them to bind to the adhesion molecules ICAM-1 and VCAM-1 that are expressed in the marginal zone (MZ) by the marginal sinus lining cells[28]
The MZ B cells express the integrins LFA-1 and α4β1 highly and this enables them to be retained within the MZ through their ability to bind to the adhesion molecules ICAM-1 and VCAM-1 expressed on surfaces of the sinus lining cells[28]
Summary
Prion diseases are a unique, infectious, neurodegenerative disorders that can affect animals and humans. We determined whether the depletion of MZ B cells from the MZ niche by blocking integrin function[28] would impede the initial delivery of prions from the blood-stream to FDC, and by doing so, reduce susceptibility to IV prion infection.
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