Plasma cells and the antibodies they secrete are essential for long-term protective immune responses and tissue homeostasis. However, they can also contribute to the pathology of numerous inflammatory and autoimmune conditions. Despite their relevance in health and disease, the mechanisms underlying antibody production and secretion are still poorly understood. This is an essential question as a better characterization of the involved molecular actors may pave the way to improved antibody production, and to the development of new therapies for antibody-driven diseases. Preliminary data obtained in our laboratory showed that the Sec22b SNARE is essential for antibody secretion but also for plasma cell maturation. Using a conditional mouse model we observed in absence of Sec22b in the B cell lineage an almost complete lack of circulating antibodies and a dramatic decrease in the number of plasma cells in the spleen and the bone marrow. We now plan to use this model to address how Sec22b affects plasma cell fitness and antibody secretion. In parallel we will determine the impact of such defects on the normal and pathological humoral immune response and on tissue homeostasis, in particular in the BM. Collectively, this project should bring new lights on the molecular mechanisms underlying antibody secretion by plasma cells, a key process with huge relevance both at the therapeutic and at the industrial levels but largely overlooked so far. Moreover, our model will allow us to study with great details the impact of plasma cells and antibodies on homeostasis and inflammation at the tissue and organism level.