Glucose-dependent de Novo Lipogenesis in B Lymphocytes

Dufort, Fay J.; Gumina, Maria R.; Ta, Nathan; Tao, Yongzhen; Heyse, Shannon A.; Scott, David A.; Richardson, Adam D.; Seyfried, Thomas N.; Chiles, Thomas C.

doi:10.1074/jbc.m114.551051

Cited by 142 publications

(74 citation statements)

References 58 publications

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“…Because FA synthesis is important for plasma B cell differentiation (Dufort et al, 2014; Fagone et al, 2007) and palmitic acid stimulates antibody production by B cells (Kunisawa et al, 2014), we examined lipid content in B cells treated with SCFAs. The lipid content of B cells was increased by SCFAs with elevated numbers of cellular lipid droplets (Figures 4E, S5D).…”

Section: Resultsmentioning

confidence: 99%

Gut Microbial Metabolites Fuel Host Antibody Responses

Kim

Qie

Park

et al. 2016

Cell Host & Microbe

623

550

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SUMMARY Antibody production is a metabolically demanding process that is regulated by gut microbiota, but the microbial products supporting B cell responses remain incompletely identified. We report that short-chain fatty acids (SCFAs), produced by gut microbiota as fermentation products of dietary fiber, support host antibody responses. In B cells, SCFAs increase acetyl-CoA and regulate metabolic sensors to increase oxidative phosphorylation, glycolysis and fatty acid synthesis, which produce energy and building blocks supporting antibody production. In parallel, SCFAs control gene expression to express molecules necessary for plasma B cell differentiation. Mice with low SCFA production due to reduced dietary fiber consumption or microbial insufficiency are defective in homeostatic and pathogen-specific antibody responses, resulting in greater pathogen susceptibility. However, SCFA or dietary fiber intake restores this immune deficiency. This B cell-helping function of SCFAs is detected from the intestines to systemic tissues and conserved among mouse and human B cells, highlighting its importance.

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Section: Resultsmentioning

confidence: 99%

Gut Microbial Metabolites Fuel Host Antibody Responses

Kim

Qie

Park

et al. 2016

Cell Host & Microbe

623

550

View full text Add to dashboard Cite

show abstract

“…Fatty acid synthesis was found to be upregulated during Toll-like receptor (TLR)-mediated DC activation, and this increased fatty acid synthesis was necessary for DC activation and their stimulation of CD8 + T cell responses 20 . Fatty acid synthesis is also key to the cell intrinsic function of T cells and B cells; synthesis of fatty acids and sterols has been shown to be necessary for cell proliferation after the activation of these cells through their antigen receptors 55,56 . Recent work demonstrated that T cell-specific deletion of acetyl-CoA carboxylase 1 (ACC1) — the rate-limiting enzyme in fatty acid synthesis — results in reduced blasting efficacy and lower accumulation of antigen-specific CD8 + T cells.…”

Section: Fatty Acid Synthesis and Immune Functionmentioning

confidence: 99%

A guide to immunometabolism for immunologists

2016

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In recent years a substantial number of findings have been made in the area of immunometabolism, by which we mean the changes in intracellular metabolic pathways in immune cells that alter their function. Here, we provide a brief refresher course on six of the major metabolic pathways involved (specifically, glycolysis, the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway, fatty acid oxidation, fatty acid synthesis and amino acid metabolism), giving specific examples of how precise changes in the metabolites of these pathways shape the immune cell response. What is emerging is a complex interplay between metabolic reprogramming and immunity, which is providing an extra dimension to our understanding of the immune system in health and disease.

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“…Activated B cells increase cell surface expression of the glucose transporter Glut1 and undergo mechanistic target of rapamycin complex 2-dependent proliferation (Caro-Maldonado et al, 2014; Doughty et al, 2006; Dufort et al, 2007; Lee et al, 2013; Woodland et al, 2008). Glucose uptake is used to fuel glycolysis, electron transport chain activity, and synthesis of lipids for expansion of the endoplasmic reticulum (Dufort et al, 2014; Garcia-Manteiga et al, 2011). X-box binding protein 1 drives expression of mitochondrial and endoplasmic reticulum biosynthesis and stress-related genes (Jang et al, 2015; Shaffer et al, 2004; van Anken et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Pyruvate Import Promotes Long-Term Survival of Antibody-Secreting Plasma Cells

et al. 2016

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Summary Durable antibody production after vaccination or infection is mediated by long-lived plasma cells (LLPCs). Pathways that specifically allow LLPCs to persist remain unknown. Through bioenergetic profiling, we found that human and mouse LLPCs could robustly engage pyruvate-dependent respiration whereas their short-lived counterparts could not. LLPCs took up more glucose than did short-lived plasma cells (SLPCs) in vivo, and this glucose was essential for the generation of pyruvate. Glucose was primarily used to glycosylate antibodies, but glycolysis could be promoted by stimuli such as low ATP levels and the resultant pyruvate used for respiration by LLPCs. Deletion of Mpc2, which encodes an essential component of the mitochondrial pyruvate carrier, led to a progressive loss of LLPCs and of vaccine-specific antibodies in vivo. Thus, glucose uptake and mitochondrial pyruvate import prevent bioenergetic crises and allow LLPCs to persist. Immunizations which maximize these plasma cell metabolic properties may thus provide enduring antibody-mediated immunity.

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Glucose-dependent de Novo Lipogenesis in B Lymphocytes

Cited by 142 publications

References 58 publications

Gut Microbial Metabolites Fuel Host Antibody Responses

Gut Microbial Metabolites Fuel Host Antibody Responses

A guide to immunometabolism for immunologists

Mitochondrial Pyruvate Import Promotes Long-Term Survival of Antibody-Secreting Plasma Cells

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