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New developments on the role of TNF-Receptor Associated Factors (TRAFs) in the etiology of chronic lymphocytic leukemia and other B cell lymphomas

AutorPérez-Chacón, Gema ; Zapata, Juan M.
Fecha de publicación2015
EditorCSIC-UAM - Instituto de Investigaciones Biomédicas Alberto Sols (IIBM)
Citación2nd Symposium on Biomedical Research (2015)
ResumenTNF-Receptor Associated Factors (TRAFs) constitute a family of trimeric adapter proteins that interact with the cytosolic region of various members of the TNF-family receptors and with components of the Toll-Like Receptors (TLRs) complexes. TRAFs function as docking molecules for proteins involved in TNFR and TLR signaling and control the extent of the response via their intrinsic E3 ubiquitin ligase activity. We have previously shown that transgenic mice with TRAF2 deficiency and enforced BCL2 expression in B lymphocytes develop small lymphocytic lymphoma (SLL) and chronic lymphocytic leukemia (CLL) with high incidence. Similar to B cells with targeted Traf2 deletion, the Traf2DN-tg mice show expanded marginal zone (MZ) B cell population and have constitutive p100 NF-κB2 processing and increased XIAP expression levels, thus relieving B cells from the need of BAFF for survival. In contrast, mice with enforced TRAF3 and BCL2 expression in B cells develop lymphadenopathies with post-Germinal Center (GC) characteristics, including syndecan-1 expression and loss of surface IgM and IgD. IHC analysis showed a variety of expanded B cell populations in spleen and nodes and severe infiltrations of organs and tissues. Immunostaining analysis show that B cell expansions with cytosolic IgG staining are common, indicative of plasmacytoma. It is noteworthy that IGHV analysis show oligoclonal expansions of B cells with unmutated IGVH recognizing PAMPs, thus further confirming our previous results indicating a role for TRAF3 in TLR-mediated B cell differentiation. Altogether, our results indicate that TRAF2 deficiency cooperates with BCL2 in promoting CLL/SLL in mice, possibly by specifically enforcing MZ B cell accumulation, increasing XIAP expression, and rendering B cells independent of BAFF for survival. In contrast, enforced TRAF3 expression in B cells favours TLR-dependent GC differentiation and plasma cell formation, and that cooperation with BCL2 causes plasmacytoma. Altogether, these results highlight the key role of TRAF-family members in controlling B cell fate.
DescripciónResumen del póster presentado al 2nd Symposium on Biomedical Research: "Advances and perspectives in cancer", celebrado en Madrid el 17 de abril de 2015.
URIhttp://hdl.handle.net/10261/152699
Aparece en las colecciones: (IIBM) Comunicaciones congresos
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