Germinal center B cells selectively oxidize fatty acids for energy while conducting minimal glycolysis.

Abstract:

:Germinal center B cells (GCBCs) are critical for generating long-lived humoral immunity. How GCBCs meet the energetic challenge of rapid proliferation is poorly understood. Dividing lymphocytes typically rely on aerobic glycolysis over oxidative phosphorylation for energy. Here we report that GCBCs are exceptional among proliferating B and T cells, as they actively oxidize fatty acids (FAs) and conduct minimal glycolysis. In vitro, GCBCs had a very low glycolytic extracellular acidification rate but consumed oxygen in response to FAs. [13C6]-glucose feeding revealed that GCBCs generate significantly less phosphorylated glucose and little lactate. Further, GCBCs did not metabolize glucose into tricarboxylic acid (TCA) cycle intermediates. Conversely, [13C16]-palmitic acid labeling demonstrated that GCBCs generate most of their acetyl-CoA and acetylcarnitine from FAs. FA oxidation was functionally important, as drug-mediated and genetic dampening of FA oxidation resulted in a selective reduction of GCBCs. Hence, GCBCs appear to uncouple rapid proliferation from aerobic glycolysis.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Weisel FJ,Mullett SJ,Elsner RA,Menk AV,Trivedi N,Luo W,Wikenheiser D,Hawse WF,Chikina M,Smita S,Conter LJ,Joachim SM,Wendell SG,Jurczak MJ,Winkler TH,Delgoffe GM,Shlomchik MJ

doi

10.1038/s41590-020-0598-4

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

331-342

issue

3

eissn

1529-2908

issn

1529-2916

pii

10.1038/s41590-020-0598-4

journal_volume

21

pub_type

杂志文章
  • The zinc-finger protein MAZR is part of the transcription factor network that controls the CD4 versus CD8 lineage fate of double-positive thymocytes.

    abstract::The CD4 versus CD8 lineage specification of thymocytes is linked to coreceptor expression. The transcription factor MAZR has been identified as an important regulator of Cd8 expression. Here we show that variegated CD8 expression by loss of Cd8 enhancers was reverted in MAZR-deficient mice, which confirms that MAZR ne...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1860

    authors: Sakaguchi S,Hombauer M,Bilic I,Naoe Y,Schebesta A,Taniuchi I,Ellmeier W

    更新日期:2010-05-01 00:00:00

  • Author Correction: Tissue patrol by resident memory CD8+ T cells in human skin.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature immunology

    pub_type: 杂志文章,已发布勘误

    doi:10.1038/s41590-020-0665-x

    authors: Dijkgraaf FE,Matos TR,Hoogenboezem M,Toebes M,Vredevoogd DW,Mertz M,van den Broek B,Song JY,Teunissen MBM,Luiten RM,Beltman JB,Schumacher TN

    更新日期:2020-06-01 00:00:00

  • Author Correction: Mechanosensing through immunoreceptors.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature immunology

    pub_type: 已发布勘误

    doi:10.1038/s41590-019-0545-4

    authors: Zhu C,Chen W,Lou J,Rittase W,Li K

    更新日期:2019-12-01 00:00:00

  • RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation.

    abstract::Stimulation of Toll-like receptors (TLRs) initiates potent innate immune responses through Toll-interleukin 1 receptor (TIR) domain-containing adaptors such as MyD88 and Trif. Analysis of Trif-deficient mice has shown that TLR3-dependent activation of the transcription factor NF-kappa B by the TLR3 ligand double-stran...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1061

    authors: Meylan E,Burns K,Hofmann K,Blancheteau V,Martinon F,Kelliher M,Tschopp J

    更新日期:2004-05-01 00:00:00

  • Autophagy and autophagy-related proteins in the immune system.

    abstract::Autophagy is an intracellular bulk degradation system that is highly conserved in eukaryotes. The discovery of autophagy-related ('ATG') proteins in the 1990s greatly advanced the mechanistic understanding of autophagy and clarified the fact that autophagy serves important roles in various biological processes. In add...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.3273

    authors: Shibutani ST,Saitoh T,Nowag H,Münz C,Yoshimori T

    更新日期:2015-10-01 00:00:00

  • Contemplating autoimmunity in the Aegean islands.

    abstract::The Greek island of Crete became host to lively discussions on immunoregulation as experts from around the world gathered for the 7th Aegean Conference on Autoimmunity in September 2015. ...

    journal_title:Nature immunology

    pub_type:

    doi:10.1038/ni.3367

    authors: Walker LS,Ziegler S,Becher B

    更新日期:2016-03-01 00:00:00

  • Egr-2 and Egr-3 are negative regulators of T cell activation.

    abstract::T cell receptor engagement in the absence of proper accessory signals leads to T cell anergy. E3 ligases are involved in maintaining the anergic state. However, the specific molecules responsible for the induction of anergy have yet to be elucidated. Using microarray analysis we have identified here early growth respo...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1193

    authors: Safford M,Collins S,Lutz MA,Allen A,Huang CT,Kowalski J,Blackford A,Horton MR,Drake C,Schwartz RH,Powell JD

    更新日期:2005-05-01 00:00:00

  • 'Educated' dendritic cells act as messengers from memory to naive T helper cells.

    abstract::Ingested antigens lead to the generation of effector T cells that secrete interleukin 4 (IL-4) rather than interferon-gamma (IFN-gamma) and are capable of influencing naive T cells in their immediate environment to do the same. Using chimeric mice generated by aggregation of two genotypically different embryos, we fou...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1077

    authors: Alpan O,Bachelder E,Isil E,Arnheiter H,Matzinger P

    更新日期:2004-06-01 00:00:00

  • A comprehensive analysis of the effects of the deaminase AID on the transcriptome and methylome of activated B cells.

    abstract::Beyond its well-characterized functions in antibody diversification, the cytidine deaminase AID can catalyze off-target DNA damage and has been hypothesized to edit RNA and mediate DNA demethylation. To comprehensively examine the effects of AID on the transcriptome and the pattern of DNA methylation ('methylome'), we...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2616

    authors: Fritz EL,Rosenberg BR,Lay K,Mihailović A,Tuschl T,Papavasiliou FN

    更新日期:2013-07-01 00:00:00

  • Costimulatory blockade by the induction of an endogenous xenospecific antibody response.

    abstract::Xenogeneic tissues induce vigorous T cell immunity, reflecting the ability of costimulatory molecules to function across species barriers. We describe a strategy to inhibit costimulation that exploits species differences using the model of porcine pancreatic islet transplantation into mice. Mice were immunized with ch...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/77853

    authors: Rogers NJ,Mirenda V,Jackson I,Dorling A,Lechler RI

    更新日期:2000-08-01 00:00:00

  • Steady-state production of IL-4 modulates immunity in mouse strains and is determined by lineage diversity of iNKT cells.

    abstract::Invariant natural killer T cells (iNKT cells) can produce copious amounts of interleukin 4 (IL-4) early during infection. However, indirect evidence suggests they may produce this immunomodulatory cytokine in the steady state. Through intracellular staining for transcription factors, we have defined three subsets of i...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2731

    authors: Lee YJ,Holzapfel KL,Zhu J,Jameson SC,Hogquist KA

    更新日期:2013-11-01 00:00:00

  • Fiber against flu.

    abstract:: ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-018-0147-6

    authors: Visan I

    更新日期:2018-07-01 00:00:00

  • Regulation of T cell receptor-alpha gene recombination by transcription.

    abstract::Despite the longstanding correlation between transcription and variable-(diversity)-joining (V(D)J) recombination, it is unknown whether transcription itself can direct recombinase targeting. Here we show that blockade of transcriptional elongation through the mouse T cell receptor-alpha (Tcra) locus suppressed V(alph...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1379

    authors: Abarrategui I,Krangel MS

    更新日期:2006-10-01 00:00:00

  • Guanylate-binding proteins convert cytosolic bacteria into caspase-4 signaling platforms.

    abstract::Bacterial lipopolysaccharide triggers human caspase-4 (murine caspase-11) to cleave gasdermin-D and induce pyroptotic cell death. How lipopolysaccharide sequestered in the membranes of cytosol-invading bacteria activates caspases remains unknown. Here we show that in interferon-γ-stimulated cells guanylate-binding pro...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-020-0697-2

    authors: Wandel MP,Kim BH,Park ES,Boyle KB,Nayak K,Lagrange B,Herod A,Henry T,Zilbauer M,Rohde J,MacMicking JD,Randow F

    更新日期:2020-08-01 00:00:00

  • Fc receptor gamma-chain, a constitutive component of the IL-3 receptor, is required for IL-3-induced IL-4 production in basophils.

    abstract::The Fc receptor common gamma-chain (FcRgamma) is a widely expressed adaptor bearing an immunoreceptor tyrosine-based activation motif (ITAM) that transduces activation signals from various immunoreceptors. We show here that basophils lacking FcRgamma developed normally and proliferated efficiently in response to inter...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1686

    authors: Hida S,Yamasaki S,Sakamoto Y,Takamoto M,Obata K,Takai T,Karasuyama H,Sugane K,Saito T,Taki S

    更新日期:2009-02-01 00:00:00

  • The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the entry of peripheral tissue T lymphocytes into afferent lymphatics.

    abstract::Although much is known about the migration of T cells from blood to lymph nodes, less is known about the mechanisms regulating the migration of T cells from tissues into lymph nodes through afferent lymphatics. Here we investigated T cell egress from nonlymphoid tissues into afferent lymph in vivo and developed an exp...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1534

    authors: Ledgerwood LG,Lal G,Zhang N,Garin A,Esses SJ,Ginhoux F,Merad M,Peche H,Lira SA,Ding Y,Yang Y,He X,Schuchman EH,Allende ML,Ochando JC,Bromberg JS

    更新日期:2008-01-01 00:00:00

  • TCR sequencing paired with massively parallel 3' RNA-seq reveals clonotypic T cell signatures.

    abstract::High-throughput 3' single-cell RNA-sequencing (scRNA-seq) allows cost-effective, detailed characterization of individual immune cells from tissues. Current techniques, however, are limited in their ability to elucidate essential immune cell features, including variable sequences of T cell antigen receptors (TCRs) that...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-019-0544-5

    authors: Tu AA,Gierahn TM,Monian B,Morgan DM,Mehta NK,Ruiter B,Shreffler WG,Shalek AK,Love JC

    更新日期:2019-12-01 00:00:00

  • Affinity for self antigen selects Treg cells with distinct functional properties.

    abstract::The manner in which regulatory T cells (Treg cells) control lymphocyte homeostasis is not fully understood. We identified two Treg cell populations with differing degrees of self-reactivity and distinct regulatory functions. We found that GITR(hi)PD-1(hi)CD25(hi) (Triple(hi)) Treg cells were highly self-reactive and c...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3522

    authors: Wyss L,Stadinski BD,King CG,Schallenberg S,McCarthy NI,Lee JY,Kretschmer K,Terracciano LM,Anderson G,Surh CD,Huseby ES,Palmer E

    更新日期:2016-09-01 00:00:00

  • Pten inactivation alters peripheral B lymphocyte fate and reconstitutes CD19 function.

    abstract::Phosphoinositide 3-kinase (PI3K) and phosphatase and tensin homolog (PTEN) phosphatase serve essential functions in the regulation of cell growth, differentiation and survival by modulating intracellular phosphatidylinositol-3,4,5-trisphosphate (PI-3,4,5-P3) concentrations. Here we show that the conditional deletion o...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni892

    authors: Anzelon AN,Wu H,Rickert RC

    更新日期:2003-03-01 00:00:00

  • The transcription factor STAT5 is critical in dendritic cells for the development of TH2 but not TH1 responses.

    abstract::Dendritic cells (DCs) are critical in immune responses, linking innate and adaptive immunity. We found here that DC-specific deletion of the transcription factor STAT5 was not critical for development but was required for T helper type 2 (TH2), but not TH1, allergic responses in both the skin and lungs. Loss of STAT5 ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2541

    authors: Bell BD,Kitajima M,Larson RP,Stoklasek TA,Dang K,Sakamoto K,Wagner KU,Kaplan DH,Reizis B,Hennighausen L,Ziegler SF

    更新日期:2013-04-01 00:00:00

  • Antigen-specific NK cell memory in rhesus macaques.

    abstract::Natural killer (NK) cells have traditionally been considered nonspecific components of innate immunity, but recent studies have shown features of antigen-specific memory in mouse NK cells. However, it has remained unclear whether this phenomenon also exists in primates. We found that splenic and hepatic NK cells from ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3227

    authors: Reeves RK,Li H,Jost S,Blass E,Li H,Schafer JL,Varner V,Manickam C,Eslamizar L,Altfeld M,von Andrian UH,Barouch DH

    更新日期:2015-09-01 00:00:00

  • Linking innate and acquired immunity: divergent role of CD46 cytoplasmic domains in T cell induced inflammation.

    abstract::CD46 is a widely expressed transmembrane protein that was initially identified as binding and inactivating C3b and C4b complement products. We used mice that were transgenic for one of two human CD46 isoforms that differ in their cytoplasmic domains (termed CD46-1 and CD46-2) to analyze the effect of CD46 stimulation ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni810

    authors: Marie JC,Astier AL,Rivailler P,Rabourdin-Combe C,Wild TF,Horvat B

    更新日期:2002-07-01 00:00:00

  • Quality of TCR signaling determined by differential affinities of enhancers for the composite BATF-IRF4 transcription factor complex.

    abstract::Variable strengths of signaling via the T cell antigen receptor (TCR) can produce divergent outcomes, but the mechanism of this remains obscure. The abundance of the transcription factor IRF4 increases with TCR signal strength, but how this would induce distinct types of responses is unclear. We compared the expressio...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3714

    authors: Iwata A,Durai V,Tussiwand R,Briseño CG,Wu X,Grajales-Reyes GE,Egawa T,Murphy TL,Murphy KM

    更新日期:2017-05-01 00:00:00

  • The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells.

    abstract::Invariant natural killer T cells (iNKT cells) are innate-like lymphocytes that protect against infection, autoimmune disease and cancer. However, little is known about the epigenetic regulation of iNKT cell development. Here we found that the H3K27me3 histone demethylase UTX was an essential cell-intrinsic factor that...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3644

    authors: Beyaz S,Kim JH,Pinello L,Xifaras ME,Hu Y,Huang J,Kerenyi MA,Das PP,Barnitz RA,Herault A,Dogum R,Haining WN,Yilmaz ÖH,Passegue E,Yuan GC,Orkin SH,Winau F

    更新日期:2017-02-01 00:00:00

  • Erratum: Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes.

    abstract::This corrects the article DOI: 10.1038/ni.3713. ...

    journal_title:Nature immunology

    pub_type: 杂志文章,已发布勘误

    doi:10.1038/ni1117-1271c

    authors: Mariño E,Richards JL,McLeod KH,Stanley D,Yap YA,Knight J,McKenzie C,Kranich J,Oliveira AC,Rossello FJ,Krishnamurthy B,Nefzger CM,Macia L,Thorburn A,Baxter AG,Morahan G,Wong LH,Polo JM,Moore RJ,Lockett TJ,Clarke JM

    更新日期:2017-10-18 00:00:00

  • Single-cell technologies for monitoring immune systems.

    abstract::The complex heterogeneity of cells, and their interconnectedness with each other, are major challenges to identifying clinically relevant measurements that reflect the state and capability of the immune system. Highly multiplexed, single-cell technologies may be critical for identifying correlates of disease or immuno...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.2796

    authors: Chattopadhyay PK,Gierahn TM,Roederer M,Love JC

    更新日期:2014-02-01 00:00:00

  • E3 ubiquitin ligase RNF128 promotes innate antiviral immunity through K63-linked ubiquitination of TBK1.

    abstract::TBK1 is essential for interferon-β (IFN-β) production and innate antiviral immunity. Here we identified the T cell anergy-related E3 ubiquitin ligase RNF128 as a positive regulator of TBK1 activation. RNF128 directly interacted with TBK1 through its protease-associated (PA) domain and catalyzed the K63-linked polyubiq...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3588

    authors: Song G,Liu B,Li Z,Wu H,Wang P,Zhao K,Jiang G,Zhang L,Gao C

    更新日期:2016-12-01 00:00:00

  • Bcl-6 mediates the germinal center B cell phenotype and lymphomagenesis through transcriptional repression of the DNA-damage sensor ATR.

    abstract::Antibody specificity and diversity is generated in B cells during germinal center maturation through clonal expansion while they undergo class-switch recombination and somatic hypermutation. Here we demonstrate that the transcriptional repressor Bcl-6 mediates this phenotype by directly repressing ATR in centroblasts ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1478

    authors: Ranuncolo SM,Polo JM,Dierov J,Singer M,Kuo T,Greally J,Green R,Carroll M,Melnick A

    更新日期:2007-07-01 00:00:00

  • Author Correction: c-Kit-positive ILC2s exhibit an ILC3-like signature that may contribute to IL-17-mediated pathologies.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature immunology

    pub_type: 已发布勘误

    doi:10.1038/s41590-019-0554-3

    authors: Bernink JH,Ohne Y,Teunissen MBM,Wang J,Wu J,Krabbendam L,Guntermann C,Volckmann R,Koster J,van Tol S,Ramirez I,Shrestha Y,de Rie MA,Spits H,Ros XR,Humbles AA

    更新日期:2020-01-01 00:00:00

  • Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages.

    abstract::Helper T cells control host defense against pathogens. The receptors for interleukin 12 (IL-12), IL-4 and IL-6 are required for differentiation into the T(H)1, T(H)2 and T(H)17 subsets of helper T cells, respectively. IL-2 signaling via the transcription factor STAT5 controls T(H)2 differentiation by regulating both t...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2030

    authors: Liao W,Lin JX,Wang L,Li P,Leonard WJ

    更新日期:2011-06-01 00:00:00