Antigen phagocytosis by B cells is required for a potent humoral response

Successful vaccines rely on activating a functional humoral response that results from promoting a proper germinal center (GC) reaction. Key in this process is the activation of follicular B cells that need to acquire antigens and to present them to cognate CD4 T cells. Here, we report that follicular B cells can phagocytose large antigen‐coated particles, a process thought to be exclusive of specialized antigen‐presenting cells such as macrophages and dendritic cells. We show that antigen phagocytosis by B cells is BCR‐driven and mechanistically dependent on the GTPase RhoG. Using Rhog^?/? mice, we show that phagocytosis of antigen by B cells is important for the development of a strong GC response and the generation of high‐affinity class‐switched antibodies. Importantly, we show that the potentiation effect of alum, a common vaccine adjuvant, requires direct phagocytosis of alum–antigen complexes by B cells. These data suggest a new avenue for vaccination approaches by aiming to deliver 1–3 μm size antigen particles to follicular B cells.