LYMPHOSIGN · Integrated study of the role of B-cell receptor signaling in the development of Follicular Lymphoma

Signaling through the B cell receptor (BCR) is central to the development and maintenance of B cells. In light of thenumerous proliferative and survival pathways activated downstream of the BCR, it comes as no surprise that malignant Bcells would co-opt this receptor to promote their own growth and survival. However, direct evidence for BCR signaling inhuman lymphoma has only come to light recently. In this proposal, I aim to better understand the role for antigen-dependent vs. antigen-dependent BCR signaling as a pathogenic mechanism in the progression of Follicular lymphoma (FL), a indolent lymphoid malignancy that retain BCR expression during malignant progression. Further investigating the intrinsic role of BCR might lead to the development of new therapeutic approaches based on the inhibition of the BCR pathways. Using an innovative loss-of -function RNA interference genetic screen together with an engineered in vitro system allowing to test FL patients's BCR reactivity and identify putative ligands, we will 1) determine whether BCR signalling in FL relies to""chronic active"" or ""tonic"" signals and 2) identify the nature of antigen(s) recognized by FL's BCR that may sustainsignalling