PXD047325

PXD047325 is an original dataset announced via ProteomeXchange.

Title	MCT1-governed pyruvate metabolism is essential for antibody class-switch recombination through H3K27 acetylation
Description	Monocarboxylate transporter 1 (MCT1) exhibits essential roles in cellular metabolism and energy supply. Although MCT1 is highly expressed in activated B cells, it is not clear how MCT1-governed monocarboxylates transportation is functionally coupled to antibody production during the glucose metabolism. Here, we report that B cell-lineage deficiency of MCT1 significantly influences the class-switch recombination (CSR), rendering impaired IgG antibody responses in Mct1f/fMb1Cre mice after immunization. Metabolic flux reveals that glucose metabolism is significantly reprogrammed from glycolysis to oxidative phosphorylation in Mct1-deficient B cells upon activation. Consistently, activation-induced cytidine deaminase (AID), is severely suppressed in Mct1-deficient B cells due to the decreased level of pyruvate metabolite. Mechanistically, MCT1 is required to maintain the optimal concentration of pyruvate to secure the sufficient acetylation of H3K27 for the elevated transcription of AID in activated B cells. Clinically, we found that MCT1 expression levels are significantly upregulated in systemic lupus erythematosus patients, and Mct1 deficiency can alleviate the symptoms of bm12-induced murine lupus model. Collectively, these results demonstrate that MCT1-mediated pyruvate metabolism is required for IgG antibody CSR through an epigenetic dependent AID transcription, revealing MCT1 as a potential target for vaccine development and SLE disease treatment.
HostingRepository	PRIDE
AnnounceDate	2023-12-14
AnnouncementXML	Submission_2023-12-14_05:15:48.490.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ligong Chen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue
Instrument	4800 Proteomics Analyzer

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-28 04:24:11	ID requested
⏵ 1	2023-12-14 05:15:48	announced

Dataset with its publication pending

submitter keyword: B cell,LC-MS/MS,A20, nuclei

Ligong Chen
contact affiliation	School of Pharmaceutical Sciences Tsinghua University
contact email	ligongchen@tsinghua.edu.cn
lab head
Ligong Chen
contact affiliation	School of Pharmaceutical Sciences Tsinghua University
contact email	ligongchen@tsinghua.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047325
     1. Label: PRIDE project
     2. Name: MCT1-governed pyruvate metabolism is essential for antibody class-switch recombination through H3K27 acetylation