Individual risk assessment of sCJD transmission during ET, using dose–effects functions ϕ₁ ( blue) and ϕ₂ ( green).

<p>A: median (vertical line within the box), the 95% CI (T bars), and the 25^th–75^th percentiles (left and right borders of the box). B: risks of iatrogenic mortality associated with other procedures.</p

The 10 components considered in the estimation of risk of iatrogenic sCJD transmission.

<p>The 10 components considered in the estimation of risk of iatrogenic sCJD transmission.</p

Population risk assessment of sCJD transmission during ET, using dose–effects functions ϕ₁ ( blue) and ϕ₂ ( green).

<p>See the legend to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0001330#pone-0001330-g002" target="_blank">figure 2</a> for the description of the box plots. The vertical line passing through both plots is the epidemic threshold (R>1).</p

PrP^c overexpression by the hematopoietic cells favors prion agent replication in the spleen of reconstituted Prp^0/0 mice.

<p>Spleen of Prp^0/0 mice lethally irradiated reconstituted with femoral bone marrow cells from Tga20 (inverse triangle) or B6 (circle) mice and inoculated with RML (black) or ME-7 (grey) strains were sampled 450 days post-inoculation and subsequently inoculated to Tga20 mice. Days post-inoculation (DPI) are represented. A <i>P</i> value of 0.001 was obtained using the Mann-Whitney t-test when comparing the Tga20→Prp^0/0 and B6→Prp^0/0 mice.</p

No difference in disease incubation period is observed in Tga20 chimeric mice inoculated with limiting doses of the RML strain (10⁻⁷ LogLD50).

<p>Tga20 mice were lethally irradiated, reconstituted with femoral bone marrow cells from B6 (square), Tga20 (triangle) or Prp^0/0 (circle) mice and inoculated with the RML prion scrapie strains. The incubation periods are expressed as days post-inoculation (DPI). At this low dose, only 7/10 mice developed scrapie. A <i>P</i> value of 0.19 was obtained using the Kruskal-Wallis ANOVA test when comparing the three groups of mice.</p

Routes of prion neuroinvasion after peripheral exposure.

<p>(a) Natural prion diseases are often acquired <i>via</i> peripheral exposure such as orally, or through skin lesions. How prion reaches its peripheral targets is not known. (b) Direct invasion of the central nervous system might occur with high doses of prion or exposure to neuroinvasive strains. (c) Whereas after exposure to limiting doses of infectivity or less neuroinvasive strains, replication in FDCs in the germinal centers of local lymphoid tissues might be necessary prior to neuroinvasion via closely associated nerve fibers. FDCs are dependent on the presence of B lymphocytes for maturation signals, such as lymphotoxin. (d) Haematogenous spread of infectivity <i>via</i> circulating bone marrow derived cells would not play a role in direct neuroinvasion.</p

Biparametric representations of B-cell maturation pathways in the lymph node.

<p>Identification of B-cell subsets in lymph node (A) and analysis of the expression of various cell surface markers versus CD27 expression (B). The specific tube of antibody combination used to analyze the expression of each marker is indicated in each graph, at the upper right. B-cell maturation is shown with arrows, drawn from the most immature. Data from one patient out of three with similar results are here represented.</p

CD24 and CD44 expression during B cell differentiation in lymph nodes.

<p>CD24 and CD44 markers define two separate subsets within germinal center B cells. Data from one patient out of three with similar results are here represented.</p

Graphical representation of the frequency (mean ± SD) of each stage of B-cell differentiation identified in the different types of samples.

<p>Samples of different anatomical sites (bone marrow, peripheral blood, lymph node and cord blood) were stained with the antibody combination of tube 1 of the panel and analyzed with the gating strategy shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0162209#pone.0162209.g002" target="_blank">Fig 2</a> in order to identify ten B-cell subsets. Cell frequency has been quantified by calculating the mean of % of cells of each subset within CD19⁺ cells (± standard deviation). HG 1: hematogones stage 1, HG 2: hematogones stage 2, IMM B: immature B cells, TR B: transitional B cells, N B: naive B cells, GC B: germinal center B cells, NM B: natural B memory cells, MM B: non-switched memory B cells, SM B: switched memory B cells, PC: plasma cells. Data from three patients for each type of sample are represented.</p

Relative expression patterns of 17 B-cell markers based on median fluorescence intensities (MFI).

<p>Means of MFI of three stage 1 or 2 hematogone samples, nine transitional B cell samples, twelve naive B cell samples, three germinal center B cell samples, nine memory B cell samples, six plasma cell samples are represented. Expression levels between different markers cannot be compared, since the measured intensity of fluorescence depends also on the specific fluorochrome bound to the antibody. HG 1: hematogones stage 1, HG 2: hematogones stage 2, TR B: transitional B cells, N B: naive B cells, GC B: germinal center B cells, M B: memory B cells, PPC: pre-plasma cells, PC: plasma cells.</p