
The diversity of the antibody repertoire plays a critical role in the defense against pathogens, but without proper regulation, the processes that promote antibody diversification can also leave patients chronically susceptible to allergies and autoimmunity. Highly-specific antibodies are produced by B cells that mature in germinal centers (GCs), which optimize antibody affinity against pathogens through iterative rounds of proliferation, mutation and selection. The research program of the Domeier laboratory aims to determine how manipulation of signaling within germinal centers influences the generation of both protective and pathogenic antibody responses. We approach our study of germinal centers in transgenic mice and human tonsil organoid cultures with a combination of advanced spectral flow cytometry, fluorescent microscopy (2-dimensional sections and 3-dimensional whole-organ imaging), and multi-omics approaches. Collectively, our research goal is to identify and characterize novel and targetable molecular pathways that amplify protective B cell immunity, while preventing the production of pathogenic autoantibodies.