The Molecular Basis of Lymphoid Architecture in the Mouse

The mammalian immune system uses numerous strategies to fulfill its principal function of defense against pathogens. At the most fundamental level, each strategy involves an antigen recognition event followed by an effector event. Receptors on cells as well as circulating host defense molecules recognize antigens on pathogens, and then through sophisticated processes that frequently involve the cooperation of numerous cell types, the pathogen is eliminated or is at least compartmentalized to prevent ongoing tissue damage. The nature of the receptors used by the immune system for antigen recognition changed dramatically during the evolution of jawed vertebrates from agnathia; compared with lower organisms, the diversity of the repertoire in all jawed vertebrates is enormous. Mechanisms that deal with the risk of self-reactivity, in large part, take place during the development of lymphocytes in the primary lymphoid organs. The ontogeny of lymphocytes in the bone marrow and thymus is resolved to fine detail, and it is clear that the molecular events regulating receptor diversification and selection according to the likelihood of self-reactivity are coregulated. The sophisticated networks of communication among different components of the immune system that are triggered by infection or immunization is equally complex. This chapter outlines the current state of knowledge of the molecular events that regulate the development and maintenance of each of these environments.