B-cell activation and signaling through TLR associated proteins (BASTA)

Fiche projet

Année

2024

Appel à projets

Appel à projets « Soutien à l'émergence de projets transfrontaliers » 2024 (Cancéropôle Est)

Acronyme

BASTA

Resumé

Chronic B-cell lymphoproliferative disorders (B-CLPD) are hematological cancers that affect adults, mostly after the age of 50. The WHO classification identifies more than twenty different entities, with variable prognosis, and some of them may remain difficult to diagnose. In this context, our group has been developing proteomic strategy aimed at highlighting new specific markers. These studies have allowed us to identify several markers such as the CD148 (DEP-1, PTPRJ), and CD180 (RP105). Our work has been recognized by the international medical community and these new markers are now used in diagnostic routine at national and international level, and CD180 is now part of the diagnostic recommendations of the new WHO 2022 classification. Interestingly, not much is known about the CD180 molecule. This protein, is a surface receptor belonging to the Toll-like receptor (TLR) family, which plays a critical role in recognizing and responding to pathogens and danger signals. CD180 is structurally similar to TLR4, but surprisingly lacks the canonical Toll/IL-1 receptor (TIR) domain required for recruitment and activation of downstream signaling pathways. In addition, the exact function of CD180 is not fully understood, but it is thought to play a role in regulating B cell activation and immune responses. However, the expression profile of TLRs in B lymphocytes and their role in the pathophysiology of B cell chronic lymphoid malignancies has not clearly established. Now, we would now like to explore the role of CD180 on both normal and pathological B cells and to determine whether this molecule may play a role in the lymphomagenesis. This project, in collaboration with Professor M. Reth from the Freiburg University, aims to decipher the signal transduction pathways in which CD180 and its interaction partners are involved, in normal and malignant B cells, and understand its potential role in lymphomagenesis and to elucidate its partners involved in signal transduction.