Application - Metabolic flux and survival in individual immune cells

Cells from the immune system display high cellular heterogeneity, and their activation is highly regulated. Following activation of immune cells, metabolic pathways are switched on/off due to the engagement in energy-demanding processes such as secretion, proliferation and differentiation. As of today, direct measurements of cellular metabolism are mostly carried out in bulk; neglecting cellular heterogeneity and sub-populations within the immune system. However, function and activation are directly linked to each individual cell, and we therefore need to assess cellular metabolism with single-cell resolution as well, and in parallel to correlate metabolic fluxes to cellular function within the immune response.

We use antibody-secreting cells (ASCs) as model system. Activation of naïve B cells leads to their differentiation into ASCs in secondary lymphoid organs. Thereby, the antibodies secreted by ASCs serve as protection. ASCs can be divided into short-lived cells that secrete large amounts of antibodies, and into long-lived cells that migrate to the bone marrow from where they secrete antibodies over years. Thus, the differentiation of B cells into one or the other category has a tremendous impact on the immediate defense as well as the duration of protection. Differentiation of quiescent naïve B cells into ASCs increases their energy demands, and antibody production and secretion enhance it further. Remarkable heterogeneity in antibody secretion rate and affinity has been demonstrated at the single-cell level. On the other hand, metabolic fluxes of ASCs are only little investigated. Our goal is to develop a technology that correlates functionality with the metabolic fluxes of individual ASCs and to study their relationship in cells from secondary lymphoid organs and bone marrow over the period of an immune response.