Metabolic microenvironments in humoral immunity

Immune responses occur in often highly compartmentalised tissue microenvironments, which in turndefine local metabolic conditions. In the architecture of lymphoid tissue, very little is known aboutcellular metabolic interactions, or how immune cells adapt their metabolism in response to a changingenvironment. The humoral immune response is essential for normal immunity, and its centrepiece isthe germinal centre (GC) reaction, which allows the generation of high-affinity antibodies and B cellmemory. The GC is tightly spatially organised in lymphoid tissue, but how this microenvironmentshapes the metabolism of GC B cells is unknown. In this project, we will explore two fundamentalquestions in B cell metabolism. GC B cells, despite dividing at the highest rate of any cell, have ahighly distinct metabolism dependent on OxPhos. Yet, the processes which maintain this are poorlyunderstood. We will examine the role of dynamic mitochondrial morphology in GC homeostasis, usingcomprehensive metabolic and immune phenotyping across multiple genetic models. In the secondaim, we will explore the effect and sensing of environmental metabolites on GC function, and howstromal cells actively regulate their metabolic microenvironment, in both health and the autoimmunedisease systemic lupus erythematosus.