Studies have reported interactions between the 3′RR, Eμ and the IgH variable region in normal and lymphomagenetic contexts 19, 20, 35, 36. Mouse models for oncogene translocations involving the IgH locus effectively produce an insight Ivacaftor cell line into the molecular mechanisms of the translocated oncogene deregulation involved in B-cell malignancies. In the case of c-myc translocation, they have revealed the key role of the 3′RR in the emergence of mature B-cell neoplasms. These mice models are relevant to human pathogenesis because the mouse 3′RR shares a strong

structural homology with the human one. Therefore, targeted inhibition of the 3′RR could theoretically provide a therapeutic strategy for the treatment of a wide range of mature B-cell lymphomas. Given the strong sequence homology between human and mouse find more 3′RR enhancers, mouse models described herein could reveal useful tools for an in vivo study of treatments based on IgH 3′RR downregulation. Christelle Vincent-Fabert and Rémi Fiancette contributed equally for this

review. This work was supported in part by a grant from « La ligue Contre le Cancer, Comité de la Corrèze et de la Haute-Vienne» and Le Lions Club de la Corrèze, Zone 33 District 103 Sud ». C. Vincent-Fabert was supported by a grant from the Association pour la Recherche sur le Cancer (ARC). Conflict of interest: The authors declare no financial or commercial conflict

of interest. “
“Suppressory B-cell function controls immune responses and is mainly dependent on IL-10 secretion. Pharmacological manipulation of B-cell-specific IL-10 synthesis could, thus, be therapeutically useful in B-cell chronic lymphocytic leukemia, transplantation, autoimmunity and sepsis. TLR are thought to play a protagonistic role in the formation of IL-10-secreting B cells. The aim of the study was to identify the molecular events selectively driving IL-10 production in TLR9-stimulated human B cells. Our data highlight the selectivity of calcineurin inhibitors in blocking TLR9-induced B-cell-derived C59 molecular weight IL-10 transcription and secretion, while IL-6 transcription and release, B-cell proliferation, and differentiation remain unaffected. Nevertheless, TLR9-induced IL-10 production was found to be independent of calcineurin phosphatase activity and was even negatively regulated by NFAT. In contrast to TLR9-induced IL-6, IL-10 secretion was highly sensitive to targeting of spleen tyrosine kinase (syk) and Bruton’s tyrosine kinase. Further analyses demonstrated increased phosphorylation of Ca2+/calmodulin kinase II (CaMKII) in TLR9-stimulated B cells and selective reduction of TLR9-induced secretion of IL-10 upon treatment with CaMKII inhibitors, with negligible impact on IL-6 levels.