1. The tetraspanin CD37 orchestrates the α(4)β(1) integrin-Akt signaling axis and supports long-lived plasma cell survival.
- Author
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van Spriel AB, de Keijzer S, van der Schaaf A, Gartlan KH, Sofi M, Light A, Linssen PC, Boezeman JB, Zuidscherwoude M, Reinieren-Beeren I, Cambi A, Mackay F, Tarlinton DM, Figdor CG, and Wright MD
- Subjects
- Animals, Antigens, CD genetics, Antigens, CD metabolism, Antigens, Neoplasm genetics, Antigens, Neoplasm metabolism, Cell Movement genetics, Cell Survival genetics, Cell Survival immunology, Germinal Center immunology, Germinal Center metabolism, Immunoglobulin G immunology, Immunoglobulin G metabolism, Integrin alpha4beta1 genetics, Integrin alpha4beta1 metabolism, Mice, Mice, Knockout, Plasma Cells metabolism, Proto-Oncogene Proteins c-akt genetics, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction genetics, Spleen immunology, Spleen metabolism, Tetraspanins genetics, Tetraspanins metabolism, Antigens, CD immunology, Antigens, Neoplasm immunology, Cell Movement immunology, Integrin alpha4beta1 immunology, Plasma Cells immunology, Proto-Oncogene Proteins c-akt immunology, Signal Transduction immunology, Tetraspanins immunology
- Abstract
Signaling by the serine and threonine kinase Akt (also known as protein kinase B), a pathway that is common to all eukaryotic cells, is central to cell survival, proliferation, and gene induction. We sought to elucidate the mechanisms underlying regulation of the kinase activity of Akt in the immune system. We found that the four-transmembrane protein CD37 was essential for B cell survival and long-lived protective immunity. CD37-deficient (Cd37(-/-)) mice had reduced numbers of immunoglobulin G (IgG)-secreting plasma cells in lymphoid organs compared to those in wild-type mice, which we attributed to increased apoptosis of plasma cells in the germinal centers of the spleen, areas in which B cells proliferate and are selected. CD37 was required for the survival of IgG-secreting plasma cells in response to binding of vascular cell adhesion molecule 1 to the α(4)β(1) integrin. Impaired α(4)β(1) integrin-dependent Akt signaling in Cd37(-/-) IgG-secreting plasma cells was the underlying cause responsible for impaired cell survival. CD37 was required for the mobility and clustering of α(4)β(1) integrins in the plasma membrane, thus regulating the membrane distribution of α(4)β(1) integrin necessary for activation of the Akt survival pathway in the immune system.
- Published
- 2012
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