PIF2025 - Characterization of the role of mitochondria in the shutdown of the adaptive immune response - (PID2024-162320OB-I00)

This thesis will investigate the molecular mechanisms that govern the termination of the adaptive immune response, with a particular focus on the role of mitochondria in regulating the duration and resolution of the germinal centre (GC) reaction. The GC is a transient microanatomical structure where B lymphocytes undergo proliferation, selection, and differentiation to generate high-affinity antibodies. Although its initiation has been well studied, the processes that define its lifespan and ensure proper shutdown remain poorly understood. Defects in this termination phase can lead to inadequate immunity, chronic inflammation, autoimmunity, or even lymphomagenesis. This project will combine genetic, metabolic, and imaging approaches to characterise how mitochondrial dynamics, bioenergetics, and stress-response pathways influence B-cell fate decisions within the GC. By identifying mitochondrial factors that control the timing and resolution of the GC response, this thesis aims to provide mechanistic insights into how the immune system preserves balance after pathogen clearance. Ultimately, these findings could contribute to the development of novel therapeutic strategies aimed at modulating immune duration in infectious diseases, autoimmune disorders, and cancer