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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Virus and Prion Research » Research » Publications at this Location » Publication #152421
Title: A POTENTIAL ROLE FOR B CELL SUBSETS IN THE PATHOGENESIS OF SCRAPIE

Author
item YOUNG, ALAN - SOUTH DAKOTA STATE UNIV
item Hamir, Amirali
item Richt, Juergen

Submitted to: Conference Research Workers Disease Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 9/10/2003
Publication Date: 11/9/2003
Citation: Young, A.J., Hamir, A.N., Richt, J.A. 2003. A potential role for B cell subsets in the pathogenesis of scrapie [Abstract]. Conference of Research Workers in Animal Diseases. p. 107.

Interpretive Summary:

Technical Abstract: Prion diseases represent a new challenge to understanding infectious disease. The causative factor of these diseases most likely is a structurally-altered, detergent-insoluble, proteinase-resistant isoform (PrPSc) of a host cellular prion protein (PrPc). PrPSc may be transmitted vertically or horizontally, i.e. via contaminated food products or transplanted tissues (including blood products and serum). Data regarding the pathogenesis, host response and diagnosis of these diseases in its natural hosts are inconclusive. In addition to nerve tissues, lymphoid cells play an important role in transmission and pathogenesis of the disease. PrPSc has been found associated with Follicular Dendritic Cells (FDCs), B cells, and Dendritic Cells (DCs) in lymph nodes and spleen. B cells (and DCs) are mobile cells, and circulate throughout the body via the bloodstream, potentially spreading the distribution of the prion protein during disease progression. Lymphoid follicles and lymph nodes have proven to be a valuable diagnostic tool in examining prion infection. We have identified a second subset of B cells which first becomes pronounced in ruminants beginning at sexual maturity, and continues to grow in size throughout adulthood. While the precise role of this large pool of blood-borne B cells remains elusive, they share phenotypic similarity to the B-1 subset found in mice and humans. More specifically, these B-1-like cells differ in the expression of complement receptors from the more conventional B-2 subset, expressing high levels of CD11b and CD11c, while simultaneously down-regulating CD21. Unlike their murine counterparts, these B-1 cells develop after birth, apparently as a result of differentiation from B-2 precursors in lymph nodes. We have examined the presence of B-1 and B-2 subsets in the blood of uninfected and infected sheep. Surprisingly, orally scrapie-infected but asymptomatic sheep expressed significantly higher numbers of B-1 cells in the peripheral blood than age-matched controls. Furthermore, elevated numbers of B-1-like cells expressing CD11c but failing to express CD11b were found in the blood of several animals, indicating a potential link between infection and production of CD11c-positive B-1 subsets in sheep. In order to further explore the potential role of these subsets in disease pathogenesis, we are developing a magnetic-bead based separation protocol for the isolation of leukocyte subsets from the blood of infected animals. Further analysis of these important subsets may yield new clues as to the pathogenesis of prion diseases in ruminants.