The homeostatic control of lymphocyte numbers provides the immune system with a basic mechanism that shapes the repertoire of the immune-competent cells and therefore, the capacity to respond to exogenous antigens as well as to maintain self-tolerance. Homeostatic mechanisms will also enable the re-establishment of the immune system following disruption (irradiation or chemotherapy). During the process of restoration, the immune system can be reset at a new equilibrium overcoming any of its previous malfunctions. This capacity of homeostatic regulation may therefore be used in potential therapeutic strategies to radically modify lymphocyte repertoires, immune responses, autoimmune disease and allergy. We now postulate that control of lymphocyte numbers may be achieved by the ability of lymphocytes to perceive the density of their own populations. Lymphocytes may use quorum-sensing mechanisms to coordinate their gene expression according to the density of their population, as long as lymphocytes have (a) a mean of assessing the number of components they interact with and (b) a standard response once a threshold number of components is detected. To address the role of quorum-sensing in the Immune System this project aims: 1) To study the role of quorum-sensing mechanisms in the homeostasis of natural activated IgM-secreting and memory B cell populations, by studying the role of secreted IgG in these processes. 2) To determine the role of quorum-sensing mechanisms associated with the homeostasis of naïve and regulatory CD4+ T cells, by studying the role of IL-2 titers in T cell homeostasis. This project has a major potential impact in medical care, addresses new lines of research and uses original experimental strategies and models that we devised in the laboratory.