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A groundbreaking study led by researchers at the Kennedy Institute of Rheumatology has revealed the significant role of asparagine, a non-essential amino acid, in regulating immune response and maintaining the balance of B cells within the body. Published in Science Immunology, the research provides new insights into the critical function of asparagine in the metabolism of germinal center (GC) B cells, which are vital for antibody production and immune defense.
B cells, which proliferate rapidly, are responsible for producing antibodies that target infections. Despite their importance, the metabolic processes that sustain these cells have remained poorly understood. The study, conducted by the Kennedy Institute team in collaboration with other researchers, sought to uncover how metabolism influences B cell function, particularly in the context of germinal centers—structures essential for refining antibodies.
The findings underscore the crucial role of asparagine in supporting GC B cell homeostasis. “When asparagine is scarce, B cells struggle, leading to weakened GC B cell function,” explained Yavuz Yazicioglu, a DPhil student at KTPS and the first author of the study.
Asparagine availability was shown to directly impact the ability of GC B cells to generate high-quality antibodies, especially during flu infection. The study found that reducing asparagine levels through diet or treatment with an asparagine-depleting drug, Asparaginase, weakened GC B cell function, resulting in lower antibody production. Furthermore, B cells with a compromised ability to produce asparagine exhibited reduced mitochondrial activity and a lack of essential metabolic building blocks like nucleotides, suggesting that asparagine is critical for maintaining the energy and resources required for effective immune responses.
The study’s lead researcher, Alex Clarke, a Wellcome Trust Clinical Research Career Development Fellow, emphasized the importance of these 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,” he noted.
The research marks a significant step forward in understanding the metabolic underpinnings of immune cell function and presents potential avenues for therapeutic intervention in immune-related diseases.
For further details, the study is published in Science Immunology, titled “Asparagine availability controls germinal center B cell homeostasis” (DOI: 10.1126/sciimmunol.adl4613).
