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The fate of T and B lymphocytes, the key cells that direct the adaptive immune response, is regulated by a diverse network of signal transduction pathways. The T- and B-cell antigen receptors are coupled to intracellular tyrosine kinases and adaptor molecules to control the metabolism of inositol phospholipids and calcium release. The production of inositol poly-phosphates and lipid second messengers directs the activity of downstream guanine-nucleo-tide-binding proteins and protein and lipid kinases/phosphatases that control lymphocyte transcriptional and metabolic programs. Lymphocyte activation is modulated bycostimulatory molecules and cytokines that elicit intracellular signaling that is integrated with the antigen-receptor-controlled pathways.