Pseudfollicles, Survival Niches for B-CLL Cells Due to NF-K B Activation Pathway
SM Rodriguez-Pinilla, B Herreros, I Castillo, P Algara, S Montes-Moreno, R Diaz de Otazu, M Perez Guillermo, MJ Mestre, C Bellas, MA Piris. CNIO, Madrid, Spain
Background: Proliferation centres (PCs) are a distinctive tissue finding in Chronic Lymphocytic Leukaemia, of unknown significance. Cell composition analysis of proliferation centres may clarify the functional relevance of this tissue compartment.
Design: A series of 75 lymph nodes in CLL cases using both tissue microarrays (TMA) and whole tissue sections have been analyzed immnuhistochemically for a large panel of markers.
Results: Specific cell subpopulations present in PCs have been identified, such as: - Dendritic cells, positive for SDF1(CXCL12), STAT1 and actin, negative for other markers of interdigitating and follicular dendritic cells. - T-cells coexpressing CD4 and CD25, partially expressing PD1, negative for FoxP3. - B-cells showing high expression of markers reporting for; proliferation (Ki67), apoptosis( Low Bcl2, High MCL1 and BIRC5), NF-kB activation (IkB-p, MUM1, TRAF1 and nuclear NFKB1) and BCR signalling (CD40, ZAP70).
Conclusions: PCs seem to constitute a distinctive tissue compartment, where NF-kB activation could take place in response to signals from specific dendritic and T-cell subpopulations. Interestingly, PC B-cells exhibit a strong expression of cytoplasmic and nuclear TRAF1, a molecule described to be induced in response to CD40 signalling by B-cells. MCL1 expression by PCs could inhibit pro-apoptotic signals from B-cell receptor mediated through NF-kB.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 112, Tuesday Morning