title: Protein kinase Cβ is critical for the metabolic switch to glycolysis following B-cell antigen receptor engagement.
abstract: Signals derived from the BCR (B-cell antigen receptor) control survival, development and antigenic responses. One mechanism by which BCR signals may mediate these responses is by regulating cell metabolism. Indeed, the bioenergetic demands of naïve B-cells increase following BCR engagement and are characterized by a metabolic switch to aerobic glycolysis; however, the signalling pathways involved in this metabolic reprogramming are poorly defined. The PKC (protein kinase C) family plays an integral role in B-cell survival and antigenic responses. Using pharmacological inhibition and mice deficient in PKCβ, we demonstrate an essential role of PKCβ in BCR-induced glycolysis in B-cells. In contrast, mice deficient in PKCδ exhibit glycolytic rates comparable with those of wild-type B-cells following BCR cross-linking. The induction of several glycolytic genes following BCR engagement is impaired in PKCβ-deficient B-cells. Moreover, blocking glycolysis results in decreased survival of B-cells despite BCR engagement. The results establish a definitive role for PKCβ in the metabolic switch to glycolysis following BCR engagement of naïve B-cells.
authors.affiliation: Department of Biology, Boston College, 140 Commonwealth Avenue, 414 Higgins Hall, Chestnut Hill, MA 02467, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Blair
authors.forename: Fay J
authors.initials: FJ
authors.lastname: Dufort
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Chiles
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D004790:Enzyme Induction; D005786:Gene Expression Regulation; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis / Q000235:genetics; D006019:Glycolysis / Q000235:genetics / Q000502:physiology*; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D064546:Protein Kinase C beta; D051745:Protein Kinase C-delta / Q000172:deficiency / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D051272:Glucose Transporter Type 1; D011947:Receptors, Antigen, B-Cell; C495678:Slc2a1 protein, mouse; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051745:Protein Kinase C-delta