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T and B lymphocytes are cells of the adaptive immune system, each of which expresses a unique antigen receptor. These cells circulate between the blood, the lymph, and, most importantly, the secondary lymphoid organs, where they survey antigen-presenting cells for their specific antigen. Once that antigen is encountered, signals from the antigen receptor activate several downstream pathways that convert quiescent naive lymphocytes into metabolically active cells that are reorganizing their actin cytoskeleton, activating transcription factors, and synthesizing a wide range of new proteins. As a result of these events, naive T and B cells undergo rapid cell division and differentiate into armed effector cells, thus expanding lymphocyte populations during an immune response and equipping these cells with the machinery to combat infections.
We begin by discussing some general principles of intracellular signaling, and then outline the pathways activated when a naive lymphocyte encounters its specific antigen. Next, we briefly discuss the co-stimulatory signaling that is necessary to activate naive T cells and, in most cases, naive B cells. In the last part of the chapter we focus on inhibitory receptors, and their roles in down-regulating signaling pathways in T and B cells.