Regulation of antigen display by Follicular Dendritic Cells in secondary lymphoid organs and beyond
Ana Martínez
CIMA, Pamplona
Antigen presentation to B cells during the germinal center (GC) response is key for the development of a robust humoral protection against pathogens. Among the antigen sources, follicular dendritic cells (FDCs) have been identified as unique stromal cells that retain and present antigens to B cells for months. However, the mechanisms by which FDCs control antigen retention remain poorly understood.
By using microscopy of clarified organs, single-cell transcriptomics, and FDC-targeting genetics, we unravelled the antigen dynamics within the B cell follicle during the humoral response. We found that the cellular heterogeneity within the FDC network, which is driven by the differential expression of complement receptor 2, orchestrates the persistence of antigens on the B cells follicles and the humoral response generated. This research line provides with key information for the generation of novel vaccines aiming to induce long-lasting B cell responses and opens new questions about the biology of FDCs under vaccination schemes and pathophysiological conditions such as cancer or autoimmune disorders.