Summary of Study ST002140
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001355. The data can be accessed directly via it's Project DOI: 10.21228/M8K70K This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002140 |
| Study Title | Mitochondrial respiration in B lymphocytes is essential for humoral immunity by controlling flux of the TCA cycle |
| Study Summary | The function of mitochondrial respiration during B cell fate decisions and differentiation 55 remained equivocal. This study reveals that selection for mitochondrial fitness occurs during B 56 cell activation and is essential for subsequent plasma cell differentiation. By expressing a 57 mutated mitochondrial helicase in transitional B cells, we depleted mitochondrial DNA during 58 B cell maturation, resulting in reduced oxidative phosphorylation. Although no changes in 59 follicular B cell development were evident, germinal centers, class switch recombination to 60 IgG, plasma cell maturation and humoral immunity were diminished. Defective oxidative 61 phosphorylation led to aberrant flux of the tricarboxylic acid cycle and lowered the amount of 62 saturated phosphatidic acid. Consequently, mTOR activity and BLIMP1 induction were 63 curtailed whereas HIF1 _and glycolysis were amplified. Exogenous phosphatidic acid 64 increased mTOR activity in activated B cells. Hence, mitochondrial function is required and 65 selected for in activated B cells for the successful generation of functional plasma cells. |
| Institute | University of Erlangen-Nürnberg |
| Department | Division of Molecular Immunology.Universitätsklinikum Erlangen, Nikolaus Fibinger Zentrum |
| Laboratory | Prof. Mielenz |
| Last Name | Mielenz |
| First Name | Dirk |
| Address | Nikolaus-Fiebiger-Zentrum, Glückstraße 6, 91054 Erlangen |
| dirk.mielenz@fau.de | |
| Phone | ++49 9131 8539105 |
| Submit Date | 2022-04-06 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS/MS(Dir. Inf.) |
| Release Date | 2022-05-02 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN003501 | AN003502 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | Ion Chromatography | None (Direct infusion) |
| Chromatography system | ThermoDionexICS3000 | TriVersa NanoMate |
| Column | ThermoDionexAS11/AG11 | TriVersa NanoMate |
| MS Type | ESI | ESI |
| MS instrument type | QTRAP | QTRAP |
| MS instrument name | ABI Sciex 3200 QTrap | ABI Sciex 6500 QTrap |
| Ion Mode | NEGATIVE | POSITIVE |
| Units | mol% | pmol/10E6 cells |
MS:
| MS ID: | MS003261 |
| Analysis ID: | AN003501 |
| Instrument Name: | ABI Sciex 3200 QTrap |
| Instrument Type: | QTRAP |
| MS Type: | ESI |
| MS Comments: | Mass spectrometric analysis was performed using the QTRAP 3200 (SCIEX) operated by Analyst 1.6.2. The electrospray ionization source parameters were −4,500 eV at 600°C, N2 gas pressures were 20 p.s.i. (curtaingas), 30 p.s.i. (gas1), and 20 p.s.i. (gas2), and collision gas was set to medium. The dwell time for ions was 75 ms, and scan time per cycle was 3.7 s.Scan ranges were from mass-to-charge ratio 87 to 606 (precursor ions) and mass-to-charge ratio 59 to 385 (product ions). Masstransitions (metabolite m/z mother ion / m/z daughter ion)recorded were as follows: UDP-glucose 565 / 323, glucose-1-phosphate 259 / 79, glucose-6-phosphate 259 / 97, 3-phosphoglycerate 185 / 97, phosphoenol pyruvate 167 / 79, citrate 191 / 87, isocitrate 191 / 111, malate 133 / 71, AMP 346/79, ADP 427/79, 2-oxoglutarate (aKG) 145 / 101, succinate 117 / 73, UDPNAG 606/385, Itaconate 129/85, Lactat 89/43, D-glucose 179/89, fumarate 115 / 71, E4P 199/97, ATP 427/79, UDP 404/79, G16BP 339/97 The contents of metabolites were calculated based on peak areas for precursor/product ion transitions relative to standards. |
| Ion Mode: | NEGATIVE |
| MS ID: | MS003262 |
| Analysis ID: | AN003502 |
| Instrument Name: | ABI Sciex 6500 QTrap |
| Instrument Type: | QTRAP |
| MS Type: | ESI |
| MS Comments: | Mass spectrometric analysis was performed using the QTRAP 6500 (SCIEX) operated by Analyst 1.6.3. The following instrument dependent settings were used: curtain gas, 20 psi; CAD gas, medium; and interface heater temperature, 100°C. PC analysis was performed in the positive ion mode by scanning for precursors of m/z 184 at a collision energy of 35 eV. PE, PS, PG, PI, and PA measurements were performed in the positive ion mode by scanning for neutral losses of 141, 185, 189, 277, and 115 D at CE of 25 eV. The value for the declustering potential was 100 V (Özbalci et al. (2013) Methods Mol Biol 1033:3-20). Scanning was performed in a mass range of m/z 650–900 D and at a scan rate of 200 D/s. 61 MCA spectra were accumulated. Mass spectra were processed by the LipidView Software Version 1.2 (SCIEX) for identification and quantification of glycerophospholipids. Endogenous glycerophospolipids were quantified by referring their peak areas to those of the internal standards. |
| Ion Mode: | POSITIVE |
