“Optional” Amino Acid Found To Shape Immune Responses

Germinal centre (GC) B cells are important for establishing immune defence. Despite having some of the highest proliferation rates among mammalian cells, their metabolism remains unusual and not fully understood. A team from the Kennedy Institute and collaborators has shed light on this critical process.

The findings, published as a research article in Science Immunology, identify the non-essential amino acid asparagine as a critical regulator of germinal centre (GC) B cell function, structures critical for refining antibodies to target infections effectively.

‘When asparagine is scarce, B cells struggle, leading to weakened GC B cell function’ said Yavuz Yazicioglu, KTPS DPhil student and first author of the study.

Reducing asparagine levels through diet or an asparagine-depleting drug, Asparaginase, weakened GC B cell function, leading to lower-quality antibody generation during flu infection, particularly from the cells with a defective capacity to produce asparagine.

‘We found when B cells were deprived of asparagine, they had reduced mitochondrial activity and building blocks such as nucleotides, suggesting asparagine sustains important metabolic processes in B cells,’ said Alex Clarke, Wellcome Trust Clinical Research Career Development Fellow. Alex further commented on the significance of their findings: ‘Our work highlights asparagine metabolism as a metabolic vulnerability in B cells that can be targeted to tackle diseases such as autoimmunity or malignancies with abnormal B cell immune responses.’

The study was funded by the Wellcome Trust, Cancer Research UK, and Versus Arthritis.

Reference: Yazicioglu YF, Marin E, Andrew HF, et al. Asparagine availability controls germinal center B cell homeostasis. Sci Immunol. 2024;9(102):eadl4613. doi: 10.1126/sciimmunol.adl4613

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