Function of the RANK-RANKL axis in FDC formation – B-stroma

Lymphoid stroma comprising endothelial and mesenchymal cells plays an increasingly recognized role in the regulation of the immune response and therefore presents novel targets for immunotherapies. Lymphatic endothelial cells activated by the TNFR-superfamily member RANK create an immune cell niche in the lymph node. We will now investigate how the activated lymphatics instruct the cellular program necessary for the differentiation of the mesenchymal stromal subset that regulates the B cell-mediated immune response. To this end, we will create a detailed molecular and cellular roadmap of developing lymph nodes in mice lacking the RANK-receptor in the lymphatics versus control mice and explore the role of innate immune cells in the differentiation of this stromal cell. We will further investigate its impact on the humoral immune response and its consequences on the formation of tertiary lymphoid structures that arise in cancer and autoimmune diseases.