Awardees

Clara Cousu  |  Reboldi Research Group  |  EMBO Postdoctoral Fellowship Award

B cells are essential immune cells that protect the host from infections via antibody production. This requires B cells to acquire e9ector functions and di9erentiate from naïve into germinal centers, and eventually into antibody-secreting plasma cells. Cell- cell interactions underpinning e9ective B cell response have been extensively studied, yet, less focus has been placed on soluble factors involved in this process, notably, mechanistic insights into lipid production and sensing on B cell immunity is still lacking. To this end, I will characterize the role of the liver X-receptors (LXR), nuclear hormone receptors regulating cholesterol homeostasis, during a B cell response. I aim to understand, with the highest granularity, how B cells integrate intrinsic and extrinsic lipid metabolic cues. Using cutting edge approaches, including conditional and inducible murine knock-out models, dietary interventions, targeted epigenetic profiling, single-cell RNA sequencing (ScRNAseq), and spatial transcriptomic to 1) Investigate LXR requirements for germinal center B cell and plasma cell di9erentiation, proliferation and maintenance in both homeostasis, vaccination and infection, in di9erent tissues; 2) Elucidate the molecular mechanisms of LXR transcriptional activity and regulation in germinal centers and antibody-secreting plasma cells; and 3) Identify the natural LXR ligand(s) that specifically shape B cell responses. My research will help resolve with high granularity how lipid metabolite sensing tunes humoral immunity in steady state and inflammation. Furthermore, it will help better understand B cell immuno-metabolic circuits that are tuned by lipid metabolites and that might be leveraged to design harmacological interventions enhancing antibody-mediated immunity.