Signal Transduction and the Coordination of B Lymphocyte Development and Function I: Transduction of BCR Signals from the Cell Membrane to the Nucleus

Proper development and differentiation of B lymphocytes is es­ sential to ensure that an organism has the ability to mount an effective humoral immune response against foreign antigens. The immune system must maintain a balance between the deletion of harmful self-reactive B cells and the generation of a diverse rep­ ertoire of B cells that has the ability to recognize an almost un­ limited array of foreign antigens. The need to delete self-reactive cells is tempered by the need to avoid the generation of large functional holes in the repertoire of foreign antigen-specific B cells that patrol the periphery. To accomplish this, the immune system must reach a compromise by eliminating only the most dangerous autoreactive clones, while allowing less harmful au­ toreactive B cells to exist in the periphery where they may com­ plement the organism's ability to mount a rapid response against invading micro-organisms. Those autoreactive cells that do enter the peripheral pool are subject to a number of conditional re­ straints that effectively attenuate their ability to respond to self­ antigens. Deleterious alterations in the homeostasis between tolerance induction and recruitment of B cells into the functional repertoire may lead to increased susceptibility to autoimmune disease or infection, respectively. Therefore, delineation of the molecular processes that maintain immunological homeostasis in the B cell compartment is critical.