Implication of Peyer’s patches dendritic cells in prion diseases.

Poster (2005, June)

Investigation of germinal centres in vivo and in vitro in the context of prion disease

Poster (2005, April)

Follicular dendritic cells innervation within spleen of five mouse strains with different incubation periods after intraperitoneal BSE inoculation.

Poster (2005, February)

Interfaces between dendritic cells, other immune cells, and nerve fibres in mouse Peyer's patches: Potential sites for neuroinvasion in prion diseases

in Microscopy Research and Technique (2005), 66(1), 1-9

In this study, we examined where immune cells and nerve fibres are located in mouse Peyer's patches, with a view to identifying potential sites for neuroinvasion by prions. Special attention was paid to ... [more ▼]

In this study, we examined where immune cells and nerve fibres are located in mouse Peyer's patches, with a view to identifying potential sites for neuroinvasion by prions. Special attention was paid to dendritic cells, viewed as candidate transporters of infectious prion. Double immunofluorescence labellings with anti-CD11c antibody and marker for other immune cells (B cells, T cells, follicular dendritic cells) were carried out and analysed by confocal microscopy on Peyer's patch cryosections. To reveal the extensive ganglionated networks of the myenteric and submucosal plexi and the sparse meshworks of nerve strands, we used antibodies directed against different neurofilament subunits or against glial fibrillary acidic protein. In the suprafollicular dome, dendritic cells connect, via their cytoplasmic extensions, enterocytes with M cells of the follicle-associated epithelium. They are also close to B and T cells. Nerve fibres are detected in the suprafollicular dome, notably in contact with dendritic cells. Similar connections between dendritic cells, T cells, and nerve fibres are seen in the interfollicular region. Germinal centres are not innervated; inside them dendritic cells establish contacts with follicular dendritic cells and with B cells. After immunolabelling of normal prion protein, dendritic cells of the suprafollicular dome are intensely positive labelled. (c) 2005 Wiley-Liss, Inc. [less ▲]

Distribution of nerve fibers and prion protein expression in mouse Peyer's patches

Poster (2004, July)

Distribution of nerve fibres and prion protein expression in mice Peyer’s patches

Poster (2003, October)

Prion pathogenesis following oral exposure is thought to involve gut-associated lymphoid tissue, which includes Peyer’s patches (PP). The antigens enter into the underlying lymphoid tissue organized in PP ... [more ▼]

Prion pathogenesis following oral exposure is thought to involve gut-associated lymphoid tissue, which includes Peyer’s patches (PP). The antigens enter into the underlying lymphoid tissue organized in PP through the medium of M cells. Infectious prion protein (PrPres) would probably take the same way of entry and like this initiate the first stage of lympho-invasion. Theoretically, intestinal lymphoid cells can come in contact with ingested PrPres and with nerve endings of the intramural system. The distribution pattern of the nerve fibres and lymphoid cells in PP and possible contact between these two elements implicated in neuroinvasion are not yet fully elucidated. In our study, classical immunoperoxydase staining and double immunofluorescence staining analysed with a confocal microscope has been carried out on C56Bl/6 mice PP. Immunoperoxidase and immunofluorescent CD11c stainings show numerous dendritic cells (DC) in the suprafollicular dome, close to the epithelium made of enterocytes and M-cells. Confocal studies show the presence of DC in the T cell zones of Peyer's patches, and also close to B cells in the follicule and to follicular dendritic cells (FDC) in the germinal centres. The PrPc expression, fundamental in the pathogenesis of prion diseases, is notably localized in germinal centres, co-localized with the FDC network and on cellular structures close to the epithelium, co-localized with DC. Nerve fibres have been immunostained in fluorescence using antibodies raised against neurofilaments High, Medium and Low and against glial fibrillary acidic protein (GFAP). Only GFAP staining revealed the presence of some nerve fibres in the suprafollicular dome, coursing the mucosal epithelium and also at the periphery of germinal centres in close connection with numerous dendritic cells. Such results permit us to postulate that these nerve fibres and PrPc positive dendritic cells, strategically positioned under the intestinal epithelium as well as in the germinal centres close to FDC network, highly expressing PrPc and thought to replicate PrPres, may be involved in the peripheral transport of the infectious prion protein. [less ▲]

FDC-B1, a new monoclonal antibody directed against bovine follicular dendrititic cells.

Poster (2003, March)

Follicular dendritic cells (FDCs) are unique immunological accessory cells located in the light and dark zones of the germinal centres in lymph follicles. Characterized by long branching processes forming ... [more ▼]

Follicular dendritic cells (FDCs) are unique immunological accessory cells located in the light and dark zones of the germinal centres in lymph follicles. Characterized by long branching processes forming a three-dimensional network, FDCs create particular microenvironments for germinal centre B and T cells and contribute to the maturation of B cells into memory cells. An involvement of the FDCs is suspected in various disorders affecting lymphoid tissues, malignant lymphoma or in some viral diseases. Moreover, in prion diseases, FDCs seem to be the major sites of extraneuronal cellular prion protein expression and the principal sites of the infectious agent accumulation in lymph organs. Because no antibody commercially available was specific to bovine FDCs, a new monoclonal antibody directed against bovine FDCs (FDC-B1) has been produced and characterized in our laboratory. The antigen detected by FDC-B1 is expressed on FDC surfaces in ruminant (bovine, ovine and caprine) lymphoid organs. This protein seems to be a membrane glycoprotein of more or less 28 kDa whose sequence will be soon determined. Moreover, FDC-B1 can be used in various applications: immunofluorescence, immunoperoxidase, immunogold labellings and western blotting. FDCs are potential targets for therapy or prophylaxis in natural TSEs, such as bovine spongiform encephalopathies and scrapie. Thus, it appears of great interest to identify bovine and ovine FDCs in routine lymphoid tissues sections. An other application of this antibody to immunofluorescence histochemistry techniques will enable the study of possible direct contacts between bovine FDCs and nerve endings and thus clarify prions neuroinvasion scheme in the case of BSE and scrapie. [less ▲]

Implication of follicular dendritic cells in prion diseases

Master of advanced studies dissertation (2002)

In prion diseases, FDCs seem to be the major sites of extraneuronal cellular prion protein (PrPc) expression and the principal sites of the infectious agent (PrPres) accumulation in lymph organs. Two ways ... [more ▼]

In prion diseases, FDCs seem to be the major sites of extraneuronal cellular prion protein (PrPc) expression and the principal sites of the infectious agent (PrPres) accumulation in lymph organs. Two ways of research has been considered: firstly, a new monoclonal antibody directed against bovine follicular dendritic cells (FDC-B1) developed in our laboratory has been characterised. We have shown that the antigen detected by FDC-B1 is expressed exclusively on FDCs surface of ruminants’ lymphoid organs. This protein seems to be a membrane glycoprotein of more or less 28 kDa whose sequence will be soon under determination. FDC-B1 will be a precious tool to detect FDC implication in scrapie infected sheep and in bovine spongiform affected cows. Secondly, the expression of PrPc isoforms has been analysed on bovine FDC depleted and enriched fractions and has been compared to bovine brain extracts. We demonstrated variation in the PrPc patterns of glycosylation between bovine FCD depleted and enriched cell populations. Moreover, glycosyl residues seemed to be different between immune and neuronal PrPc. As interaction of PrPc and PrPres appears to be a crucial pathogenic step promoted by homology, variation in PrPc glycoforms could explain the absence of infectivity in most bovine lymph organs affected by bovine spongiform encephalopathy. [less ▲]