Pathogenic antibodies crucially contribute to the pathogenesis of multiple diseases including systemic lupus erythematosus. Refractory diseases may be caused by antibody secretion from long-lived plasma cells (PC). We found that PC in inflamed kidneys are characterized by metabolic adaptations and sustain inflammation by predominant secretion of FcγR-activating hyposialylated IgG2a. Further, we identified a novel putative autoimmune-related TACIlo PC population, which we will analyze regarding origin, phenotypic, metabolic and functional patterns. To selectively target pathogenic PC we will develop new strategies of modulating intracellular signaling and induction of apoptosis.
DFG Programme
CRC/Transregios