Development and homeostasis of long-lived plasma cells

The immune system's protective memory consists of 'humoral' antibodies secreted by plasma cells in body fluids, which provide long-term protection against pathogens against which an immune reaction has occurred (for a review, see Ahmed and Gray 1996). Since the half-life of antibodies in serum is only a few days (Vieira and Rajewsky 1988), new antibodies must be secreted continuously. Using a newly developed technology for identifying and isolating living plasma cells based on the antibodies they secrete (Manz et al., 1995), our research group recently demonstrated, surprisingly and for the first time, that antibody-secreting plasma cells have a lifespan in vivo similar to that of memory B cells (Manz et al. 1997). We (Manz et al., 1998) and others (Slifka et al., 1998a, 1998b) have also shown that these long-lived plasma cells are responsible for protective immunological memory. Within the framework of this project, we aim to apply our technology to the molecular analysis of induction, homing, and survival of long-lived plasma cells. Knowledge of the molecules regulating these processes is essential for understanding immunoprotection, the etiopathogenesis of allergies and autoimmune diseases, and the development of vaccination strategies.