Project Details
Projekt
Metabolic regulation of plasma cell function and antibody glycosylation
Subject Area
Immunology
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 505372148
Plasma cells (PC) can produce up to 10,000 antibodies per second. Such high protein synthesis with subsequent N-glycosylation at the Fc part requires a special adaptation of the PC metabolism. Besides protective antibodies, PC can also produce pathogenic antibodies which contribute to the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). In comparison to short-lived PC, long-lived PC display a strongly increased glucose uptake, which primarily provides substrates for antibody glycosylation rather than for ATP generation. IgG glycosylation at Asn297 critically determines half-life and effector function of IgG, including affinity to different Fc gamma receptors, and therefore, pro- versus anti-inflammatory properties. Our overarching aim is to understand how signals in the autoimmune/inflammatory context modulate PC phenotype, metabolism, resistance and function including antibody synthesis and glycolsylation. We hypothesize that PC within inflamed, presumably hypoxic organs use different metabolic pathways compared to PC within a non-inflammatory environment. Metabolic adaptations may decrease IgG glycosylation, especially sialylation, thereby fostering inflammation. Based on the metabolic profiling of PC subsets we will develop new therapeutic strategies to treat autoimmune diseases, for instance by selectively interfering with metabolic pathways in predominantly pathogenic PC subsets.
DFG Programme
Research Units
