Molecular interactions controlling immune homeostasis in the marginal zone

The immune system serves to eliminate harmful microorganisms and cancer cells from the body. When these agents invade the blood stream, rapid detection and response by immune cells is crucial to protect the host. To achieve this, different immune cells such as B cells and dendritic cells are organized in a unique structure in the spleen where blood is filtered: the marginal zone. Generally speaking, marginal zone B cells will rapidly produce antibodies that neutralize harmful bacteria, while dendritic cells will mount a long-lasting and tailored immune response against a broad spectrum of agents. However, the precise factors that control the development and function of cells in the marginal zone remain poorly characterized. A better understanding of the biology of cells in this compartment may lead to novel approaches in the treatment of invasive infections, autoimmune disease and cancer. In this thesis, I report how the development of B cells and dendritic cells in the marginal zone depends on the relatively unknown protein TAOK3. In addition, we found that innate lymphoid cells, another type of immune cells, provided biological signals that were crucial for the development of marginal zone dendritic cells. Furthermore, we revealed that dendritic cells in the spleen protect against a chronic myeloid leukemia-like disease through the expression of the protein IRF8. In summary, we have uncovered novel biological factors that regulate the development and function of immune cells in the spleen