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

By Ana Martínez-Riaño, Pilar Delgado, Pilar Mendoza, Clara L Oeste, David Abia, Elena Rodríguez-Bovolenta, Martin Turner, Balbino Alarcón

Posted 27 Feb 2020
bioRxiv DOI: 10.1101/2020.02.26.965921

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.

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