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Blood, 1 June 2006, Vol. 107, No. 11, pp. 4458-4465. Prepublished online as a Blood First Edition Paper on January 31, 2006; DOI 10.1182/blood-2005-12-4788. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-12-4788v1 107/11/4458    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Doughty, C. A. Articles by Chiles, T. C. Search for Related Content PubMed PubMed Citation Articles by Doughty, C. A. Articles by Chiles, T. C. Related Collections Signal Transduction Immunobiology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Antigen receptor–mediated changes in glucose metabolism in B lymphocytes: role of phosphatidylinositol 3-kinase signaling in the glycolytic control of growth Cheryl A. Doughty, Blair F. Bleiman, Dean J. Wagner, Fay J. Dufort, Jennifer M. Mataraza, Mary F. Roberts, and Thomas C. Chiles From the Departments of Biology and Chemistry, Boston College, Chestnut Hill, MA. The bioenergetic response of B lymphocytes is subject to rapid changes following antigen encounter in order to provide ATP and anabolic precursors necessary to support growth. However, the pathways involved in glucose acquisition and metabolism are unknown. We find that B lymphocytes rapidly increase glucose uptake and glycolysis following B-cell antigen receptor (BCR) crosslinking. Inhibition of glycolysis blocks BCR-mediated growth. Prior to S-phase entry, glucose metabolism shifts from primarily glycolytic to include the pentose phosphate pathway. BCR-induced glucose utilization is dependent upon phosphatidylinositol 3-kinase (PI-3K) activity as evidenced by inhibition of glucose uptake and glycolysis with LY294002 treatment of normal B cells and impaired glucose utilization in B cells deficient in the PI-3K regulatory subunit p85. Activation of Akt is sufficient to increase glucose utilization in B cells. We find that glucose utilization is inhibited by coengagement of the BCR and FcRIIB, suggesting that limiting glucose metabolism may represent an important mechanism underlying FcRIIB-mediated growth arrest. Taken together, these findings demonstrate that both growth-promoting BCR signaling and growth-inhibitory FcRIIB signaling modulate glucose energy metabolism. Manipulation of these pathways may prove to be useful in the treatment of lymphoproliferative disorders, wherein clonal expansion of B lymphocytes plays a role. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: PI-3K controls B cells' sweet tooth Laurence Morel Blood 2006 107: 4201-4202. [Full Text] [PDF] This article has been cited by other articles: S. R. Jacobs, C. E. Herman, N. J. MacIver, J. A. Wofford, H. L. Wieman, J. J. Hammen, and J. C. Rathmell Glucose Uptake Is Limiting in T Cell Activation and Requires CD28-Mediated Akt-Dependent and Independent Pathways J. Immunol., April 1, 2008; 180(7): 4476 - 4486. [Abstract] [Full Text] [PDF] J. A. Wofford, H. L. Wieman, S. R. Jacobs, Y. Zhao, and J. C. Rathmell IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival Blood, February 15, 2008; 111(4): 2101 - 2111. [Abstract] [Full Text] [PDF] F. J. Dufort, B. F. Bleiman, M. R. Gumina, D. Blair, D. J. Wagner, M. F. Roberts, Y. Abu-Amer, and T. C. Chiles Cutting Edge: IL-4-Mediated Protection of Primary B Lymphocytes from Apoptosis via Stat6-Dependent Regulation of Glycolytic Metabolism J. Immunol., October 15, 2007; 179(8): 4953 - 4957. [Abstract] [Full Text] [PDF] A. Kiely, N. H McClenaghan, P. R Flatt, and P. Newsholme Pro-inflammatory cytokines increase glucose, alanine and triacylglycerol utilization but inhibit insulin secretion in a clonal pancreatic {beta}-cell line J. Endocrinol., October 1, 2007; 195(1): 113 - 123. [Abstract] [Full Text] [PDF] Y. Zhao, B. J. Altman, J. L. Coloff, C. E. Herman, S. R. Jacobs, H. L. Wieman, J. A. Wofford, L. N. Dimascio, O. Ilkayeva, A. Kelekar, et al. Glycogen Synthase Kinase 3{alpha} and 3{beta} Mediate a Glucose-Sensitive Antiapoptotic Signaling Pathway To Stabilize Mcl-1 Mol. Cell. Biol., June 15, 2007; 27(12): 4328 - 4339. [Abstract] [Full Text] [PDF] S. G. Rudrappa and B. D. Humphrey Energy Metabolism in Developing Chicken Lymphocytes Is Altered during the Embryonic to Posthatch Transition J. Nutr., February 1, 2007; 137(2): 427 - 432. [Abstract] [Full Text] [PDF]

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