Recreation of an antigen-driven germinal center in vitro by providing B cells with phagocytic antigen

Successful vaccines rely on activating a functional humoral response that results from generating class-switched high affinity immunoglobulins (Igs) with a superior capacity to neutralize infection. Key to this process is the germinal center (GC) reaction, in which B cells are selected in their search for antigen and T cell help. A major hurdle to understanding the mechanisms of B cell:T cell cooperation has been the lack of an in vitro system to recreate GCs in an antigen-specific manner. Here we report the generation of functional antigen-specific high affinity Igs of different isotypes in simple 2-cell type cultures of naive B and T cells. It is crucial for this process for B cells to take up antigen by a phagocytic mechanism, which results in stronger and more sustained BCR signals compared to stimulation with a soluble antigen. We also show the applicability of the system to generate antibodies of potential clinical interest.