Regulation of splenic B cell responses by tissue resident macrophages. (360G-Wellcome-106245_Z_14_Z)

A major challenge for the immune system is to protect against a wide range of pathogens without causing harm to the host. To reach this balance, it is critical that infections are quickly detected and that information regarding the type and location of the challenge is transmitted to other immune cells. Macrophages play a central role in processing and delivering such information and are often positioned in strategic locations within lymphoid organs guarding entry and exit ports. The spleen is t he largest secondary lymphoid organ and is critical for protection from blood-born pathogens. Newly arriving B cells and blood-carried antigens enter the spleen via the marginal-zone, an important area of cellular trafficking and information exchange. In this compartment, specialized macrophage subsets have been described. These cells capture both host-derived and foreign antigens and are found in close association with circulating follicular B cells. In this proposal, we will use advanced intra vital imaging techniques and generate novel mouse models to explore the mechanisms employed by these splenic macrophages to regulate B cell trafficking, activation and differentiation. Insights gained through these studies may aid in the design of new regimes for vaccination and for treatment of immunological disorders.