f many cancer cells. B cells have also been shown to increase PG 490 web glucose metabolism upon stimulation. The details and relevance of this B cell metabolic transition from quiescence to activation, however, are not understood. Here we examined the glycolytic and mitochondrial metabolism of resting and stimulated normal, anergic, or chronically BAFF-stimulated and autoimmune prone B cells. Activation of normal B cells led to broadly increased metabolism but decreased lipid oxidation. Interestingly, unlike T cells or macrophages, normal B cells do not readily transition to a glycolytic metabolism and instead increase metabolism without specific shifts in the balance of lactate production to oxygen consumption. Anergic B cells appeared metabolically suppressed and failed to increase either aerobic glycolysis or mitochondrial oxidative metabolism upon stimulation. Conversely, B cells chronically exposed to high levels of BAFF were poised for rapid induction of aerobic glycolysis and metabolic reprogramming. These metabolic changes were essential for proliferation and 
antibody production, as pharmacologic inhibition of glycolysis or genetic deletion of Glut1 impaired B cells and suppressed antibody production following immunization. Thus, B cells share some features with the metabolic transition of activated T cells and are glycolysis-dependent, but respond differently than T cells to activating signals or have an intrinsically different metabolic program that can be modified by tolerance and autoreactivity. A key feature of B cell activation through either the BCR or TLR4 is to induce cell growth, proliferation, and antibody production. Despite the distinct signaling mechanisms of BCR and TLR4, B cells underwent similar metabolic reprogramming. Catabolic metabolism, such as lipid oxidation, PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19845667 sharply decreased and cell growth was favored. Aerobic glycolysis has been shown to provide cancer cells and activated T cells with biosynthetic intermediates and to play a central feature in the rapid growth of these cells. Consistent with previous reports, we found that B cells also increased glycolysis upon activation. However in contrast to T cells, B cells started with higher rates of glycolysis and activated B cells proportionally increased mitochondrial oxygen consumption to maintain a balanced glycolytic and oxidative metabolism. The basis for increased oxygen consumption and J Immunol. Author manuscript; available in PMC 2015 April 15. Caro-Maldonado et al. Page 10 oxidative metabolism is likely through increased glucose and glutamine oxidation, as lipids are conserved for cell growth rather than consumed for energy production. Surprisingly, however, efficient mitochondrial electron transport was not essential for antibody production. The role of mitochondrial metabolism in B cell activation and function remains uncertain, but differences from T cells or macrophages suggest that alternate signaling pathways contribute to B cell metabolic reprogramming, or that B cells have intrinsic metabolic distinctions. It is evident that B cell metabolic reprogramming depends in part on cMyc. In T cells, HIF1 was shown dispensable while cMyc was required for upregulation of glycolytic genes, including Glut1, upon activation. B cells were similarly found to be independent of HIF1 but reliant on cMyc upregulation to increase glycolysis. Also like T cells, cMyc did not regulate all mitochondrial metabolic pathways, as lipid oxidation decreased and pyruvate oxidation