Project Details
Projekt
Spatiotemporal dynamics of calcium signaling and metabolism in germinal center B cells
Subject Area
Immunology
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 505372148
As the site of affinity maturation for the humoral immune response, the germinal center constitutes an important checkpoint for B cell fate decisions in secondary lymphatic organs. Germinal centers provide compartmentalized microenvironments, physically separating antigen-induced B cell receptor activation and affinity-based selection from B cell division linked to somatic hypermutation. The cellular exchange between both germinal center compartments is highly dynamic. Furthermore, activation via the B cell receptor is known to induce profound changes in the metabolic status of B cells, and it has been proposed to trigger a “metabolic clock”, setting a time window during which B cells have to receive a second signal to survive, such as T cell help. Intravital microscopy has significantly contributed to our understanding of germinal center dynamics. However, neither the mechanism of spatiotemporal regulation at the intersection between B cell receptor signaling and metabolism in the germinal center, nor the consequences for B cell selection, proliferation and differentiation are well understood. This is partly due to the lack of tools for analyzing B cell metabolism and function at a single cell level in vivo. Using our unique imaging tools, we plan to (i) determine the relation between cytoplasmic calcium and general metabolic activity in germinal center B cells in vivo, (ii) assess how NAD(P)H-dependent metabolic pathways, particularly reactive oxygen species-producing NADPH oxidases, are involved in germinal center selection events, and (iii) define the impact of metabolic microenvironments within the different germinal center zones on B cell activation. This project will for the first time deliver correlative data on calcium signaling and metabolic activity of germinal center B cells in vivo, and assess the impact of the microenvironment on the crosstalk of B cell receptor signaling and metabolism under physiological conditions. Within the research unit, we will benefit from the excellent environment providing knowledge on B cell metabolism and signaling. This complements our expertise on in vivo metabolic and functional imaging of germinal center B cells, which will be made available to the members of the consortium.
DFG Programme
Research Units
