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.
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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.
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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.
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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).
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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
Chercheur : Valérie DEFAWEUX