Les Cellules Folliculaires Dendritiques : implication dans les maladies à prion
Follicular dendritic cells (FDCs) are peculiar stromal cells mainly located in the light zone of the germinal centres of the lymph follicles. They are characterised by long branching processes forming a three-dimensional network. These cells have been described as immunological accessory cells (Heinen et al., 1988; Maeda et al., 1995) with typical morphological characteristics and cytochemical and immunological phenotypes (Heinen et al., 1984). Their origin has not been unequivocally established yet. Several data support the hypothesis that FDCs differentiate from precursor cells, sharing features with mesenchymal or fibroblastic cells (Bosseloir et al., 1994). FDCs are major components of the dynamic germinal centre and are essential for generating an effective and complete humoral immune response (Heinen et al., 1995; Kosco et al., 1992). Thanks to their ability to trap antigens in the form of immune complexes via Fc or C3b receptors for long periods of time, FDCs provide a particular microenvironment for germinal centre B and T cells that influences cell activation and proliferation and B cells maturation into memory cells (Heinen et al., 1985). Mature follicular dendritic cells (FDCs) were suggested as having a key-role in the accumulation and replication of prions (Kitamoto et al, 1991). Early studies showed that whole body gamma irradiation of mice failed to influence prion pathogenesis or incubation time arguing in favour of a significant involvement of non-proliferating cells in the lymphoreticular phase of prion propagation (Fraser et al., 1987). Moreover, no infectivity has been recovered in the spleens of intraperitoneally inoculated mice with lack of identifiable FDCs in their spleen (Mabbott et al., 2000). In the same way, switching off FDCs by treating mice with soluble lymphotoxin-b receptor or TNF receptor abolishes splenic prion accumulation and retards neuroinvasion (Montrasio et al., 2000; Mabbot et al., 2002).

Different studies having this in focus have been carry out.

The different aspects taken into account were (1) the characterization of the immunological responses, and (2) the analysis of  the ultrastructure and the functional ability of FDC infected with 139A scrapie strain.

The production and characterisation of a new mouse monoclonal antibody directed against bovine follicular dendritic cells (FDC-B1) is reported. The antigen detected by FDC-B1 is expressed exclusively on the surface of FDCs in ruminant lymphoid organs. The antigen has an approximate molecular weight of 28 kDa.

PrPc expression (glycoforms and truncatures), pre-requisite for the development of TSE (Blattler et al. 1997) on the surface of bovine and human are compared in order to study the differences in the pathogenesis of BSE and vCJD. This work is done in collaboration with Professor Piero Parchi from the University of Bologna (Italy).

To analyse the features limiting TSE infectivity to bovine ileal Peyer’s patches keeping in mind that jejunal Peyer’s patches are than not infectious (Terry et al., 2003), we study PrPc expression and innervation in ileal and jejunal Peyer’s patches in bovines. A particular attention was given to Peyer’s patches specific compartments related to TSE pathogenesis: the site of entry (epithelium associated follicles), the potential transfer areas of infectious agent (lamina propria, suprafollicular dome, the interfollicular zone), the retention areas (germinal centres and FDCs), the localization of nerve fibres likely to be involved in the transmission of the agent to central nervous system.

Promoteur : Ernst HEINEN

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