A study conducted by researchers at the Kennedy Institute of Rheumatology has uncovered a pivotal role of asparagine metabolism in regulating B cell homeostasis and immune response.

Germinal center (GC) B cells are responsible for producing antibodies. The cells have some of the highest proliferation rates of all mammalian cells, yet their metabolism is unusual and incompletely understood, so a team from the Kennedy Institute and collaborators set out to understand more.

The findingspublished in Science Immunologyidentify the non-essential amino acid asparagine as a critical regulator of germinal center (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.

Clarke further commented on the significance of their findings, saying, “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.”