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Homeostatic control of lymphocyte survival: potential origins and implications

Nature Immunology volume 3, pages 515–521 (2002)Cite this article

Abstract

Lymphocytes depend on extracellular ligands to maintain their viability. Structurally diverse lymphocyte receptors transmit survival signals through separate signal transduction cascades, which all share the ability to sustain viability by maintaining the sequestration of apoptogenic factors within mitochondria. Receptors can induce cellular survival either by promoting the expression and/or function of anti-apoptotic Bcl-2 family proteins or by activating the phosphatidylinositol-3 kinase–Akt pathway. Either of these events represses the function of the pro-apoptotic proteins Bax and Bak, which are required for mitochondrial release of cytochrome c. As we discuss here, the apparently redundant functions of Bax and Bak may have evolved to prevent lymphocyte mitochondria from adapting to loss of receptor–mediated signal transduction and thus keep lymphocytes from accumulating in a cell-autonomous manner.

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Figure 1: Induction of apoptosis upon loss of ligands for survival receptors.
Figure 2: Receptors can promote survival by stimulating glucose metabolism.
Figure 3: Receptor control of glycolysis and survival through Akt.

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  1. Abramson Family Cancer Research Institute and Department of Cancer Biology, University of Pennsylvania, Philadelphia, 19104, PA, USA

    David R. Plas, Jeffrey C. Rathmell & Craig B. Thompson

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Plas, D., Rathmell, J. & Thompson, C. Homeostatic control of lymphocyte survival: potential origins and implications. Nat Immunol 3, 515–521 (2002). https://doi.org/10.1038/ni0602-515

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