B-cell–receptor (BCR) engagement regulates glucose intake and utilization. (1) Antigen (Ag) binding triggers BCR signaling and (2) activation of phosphatidylinositol 3-kinase (PI-3K) and its p85α subunit. (3) This in turns activates AKT by recruiting it to the membrane. AKT has multiple effects on glucose transport and utilization: (3a) it increases Glut1 expression, which results in increased glucose intake and (3b) it increases glucose catabolism through glycolysis and the pentose phosphate pathway, (3c) to the expense of oxidative phosphorylation through the TCA cycle, which is the main pathway to generate ATP in resting lymphocytes. (4) All of these concerted events concur to greatly boost ATP production, which is necessary to fuel cell growth and proliferation. (5) Conversely, engagement of the negative regulator FcγRIIb by immune complexes results in the opposite PI-3K–mediated effects on glucose intake and utilization, starving B-cell proliferation of its energy supply. Illustration by Kenneth Probst.