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MCT1-governed pyruvate metabolism is essential for antibody class-switch recombination through the acetylation of H3K27

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE247204 | GEO | 2023/11/22

REPOSITORIES: GEO

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MCT1-governed pyruvate metabolism is essential for antibody class-switch recombination through H3K27 acetylation.

Project description: Not available

| S-EPMC10762154 | biostudies-literature

MCT1-governed pyruvate metabolism is essential for antibody class-switch recombination through H3K27 acetylation

Project 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.

2023-12-14 | PXD047325 | Pride

MCT1-governed pyruvate metabolism is essential for antibody class-switch recombination through the acetylation of H3K27

Project description:MCT1-governed pyruvate metabolism is essential for antibody class-switch recombination through the acetylation of H3K27

| PRJNA1036618 | ENA

Stag2-mediated chromatin dynamics regulates antibody class switch recombination

Project description:This SuperSeries is composed of the SubSeries listed below.

2026-05-20 | GSE312233 | GEO

Processing of switch transcripts is required for targeting of antibody class switch recombination.

Project description: Not available

| S-EPMC2212419 | biostudies-literature

Mlh1 can function in antibody class switch recombination independently of Msh2.

Project description: Not available

| S-EPMC2193780 | biostudies-literature

Stag2-mediated chromatin dynamics regulates antibody class switch recombination [RNA-Seq]

Project description:Class switch recombination (CSR) in B lymphocytes generates different functional antibody isotypes and cohesin-mediated chromatin loop extrusion is proposed to promote CSR. However, the detailed regulatory mechanism of cohesin in CSR is largely lacking. Here, we revealed that Stag2 is a specific cohesin regulator playing critical roles in promoting CSR. Stag2-deficiency, not Stag1-deficiency, significantly decreases the interaction of acceptor CH with CSR center, leading to decreased transcription of acceptor CH and impaired CSR. Notably, Stag2 could compensate for Stag1 binding within Igh upon Stag1-deficiency, while Stag2-deficiency significantly decreases Stag1 binding within Igh. Interestingly, Stag2 expression is higher than Stag1 during germinal center (GC) B cell development and Stag2 expression has a high correlation with CSR level in GC B cells upon vaccination and SARS-Cov-2 infection. Furthermore, Stag2 is also highly expressed in GC B cells within different tumors, corresponding to the high level of CSR in tumors. Altogether, our findings uncover the unrecognized specific roles of Stag2 in regulating CSR during physiological and pathological immune responses.

2026-05-20 | GSE312230 | GEO

Stag2-mediated chromatin dynamics regulates antibody class switch recombination [ChIP-Seq]

2026-05-20 | GSE312228 | GEO

Stag2-mediated chromatin dynamics regulates antibody class switch recombination [3C-HTGTS]

2026-05-20 | GSE312226 | GEO

Stag2-mediated chromatin dynamics regulates antibody class switch recombination [PRO-Seq]

2026-05-20 | GSE312229 | GEO