GLUT1-mediated glucose import in B cells is critical for anaplerotic balance and humoral immunity.
Cell Rep
; 43(2): 113739, 2024 Feb 27.
Article
em En
| MEDLINE
| ID: mdl-38340319
ABSTRACT
Glucose uptake increases during B cell activation and antibody-secreting cell (ASC) differentiation, but conflicting findings prevent a clear metabolic profile at different stages of B cell activation. Deletion of the glucose transporter type 1 (GLUT1) gene in mature B cells (GLUT1-cKO) results in normal B cell development, but it reduces germinal center B cells and ASCs. GLUT1-cKO mice show decreased antigen-specific antibody titers after vaccination. In vitro, GLUT1-deficient B cells show impaired activation, whereas established plasmablasts abolish glycolysis, relying on mitochondrial activity and fatty acids. Transcriptomics and metabolomics reveal an altered anaplerotic balance in GLUT1-deficient ASCs. Despite attempts to compensate for glucose deprivation by increasing mitochondrial mass and gene expression associated with glycolysis, the tricarboxylic acid cycle, and hexosamine synthesis, GLUT1-deficient ASCs lack the metabolites for energy production and mitochondrial respiration, limiting protein synthesis. We identify GLUT1 as a critical metabolic player defining the germinal center response and humoral immunity.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
/
Imunidade Humoral
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Alemanha