Age-related changes in B cell metabolism.

Area of Science:

• Immunology
• Cellular Metabolism
• Aging Research

Background:

• Antibody production by B cells is crucial for vaccine efficacy.
• Immune responses, including antibody production, are known to decline with age.
• The underlying cellular mechanisms contributing to age-related immune decline require further elucidation.

Purpose of the Study:

• To investigate the role of metabolic changes in B cells contributing to the attenuated antibody responses observed in aged humans following influenza vaccination.

Main Methods:

• Analysis of B cell mitochondrial function, including reactive oxygen species (MROS) and mitochondrial mass (MM).
• Assessment of metabolic pathways such as glycolysis and oxidative phosphorylation using Seahorse analysis.
• Transcriptome analysis to identify defects in metabolic pathways, including one-carbon metabolism.

Main Results:

• Aging altered mitochondrial function in B cells, increasing MROS and MM in some subsets while decreasing expression of SIRT1, FOXO1, and CPT-1.
• Aged B cells exhibited minor defects in glycolysis but significant reductions in oxidative phosphorylation post-activation.
• Transcriptome analysis revealed pronounced defects in one-carbon metabolism, essential for amino acid and nucleotide synthesis.

Conclusions:

• Metabolic alterations, particularly mitochondrial dysfunction and impaired one-carbon metabolism, are evident in aged B cells.
• The reduced capacity of aged B cells to enhance their metabolism upon activation contributes to weakened antibody responses in the elderly.
• These findings highlight metabolic reprogramming as a key factor in age-related immunosenescence and reduced vaccine effectiveness.