The Tetraspanin CD37 Orchestrates the alpha4beta1 Integrin-Akt Signaling Axis and Supports Long-Lived Plasma Cell Survival
until further notice
SourceScience Signaling, 5, 250, (2012), pp. ra82
Article / Letter to editor
Display more detailsDisplay less details
Laboratory of Hematology
SubjectNCMLS 1: Infection and autoimmunity; NCMLS 2: Immune Regulation; NCMLS 2: Immune Regulation ONCOL 3: Translational research; ONCOL 3: Translational research NCMLS 2: Immune Regulation
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 alpha(4)beta(1) integrin. Impaired alpha(4)beta(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 alpha(4)beta(1) integrins in the plasma membrane, thus regulating the membrane distribution of alpha(4)beta(1) integrin necessary for activation of the Akt survival pathway in the immune system.
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.