Unraveling the Secret Shapes of Optional Amino Acids in Boosting Immune Defense

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Germinal center (GC) B cells play a crucial role in establishing immune protection. Although they exhibit some of the highest rates of proliferation among mammalian cells, their metabolism remains peculiar and not entirely comprehended. A research team from the Kennedy Institute and its collaborators has illuminated this vital procedure.

The results, published as a research article in Science Immunology, pinpoint the non-essential amino acid asparagine as a significant regulator of germinal center (GC) B cell functionality, structures essential for refining antibodies to effectively target infections.

‘When asparagine is low, B cells face challenges, causing diminished GC B cell functionality’ stated Yavuz Yazicioglu, KTPS DPhil student and primary author of the research.

Lowering asparagine levels through dietary changes or via an asparagine-depleting drug, Asparaginase, impaired GC B cell functionality, resulting in lower-quality antibody production during influenza infection, particularly from the cells lacking the ability to generate asparagine.

‘Our findings revealed that when B cells were deprived of asparagine, they exhibited diminished mitochondrial activity and building blocks like nucleotides, indicating asparagine is crucial for sustaining essential metabolic functions in B cells,’ remarked Alex Clarke, Wellcome Trust Clinical Research Career Development Fellow. Alex further elaborated on the importance of their discoveries: ‘Our research emphasizes asparagine metabolism as a metabolic weakness in B cells that can be strategically targeted to address conditions like autoimmunity or cancers exhibiting abnormal B cell immune responses.’

The research received funding from the Wellcome Trust, Cancer Research UK, and Versus Arthritis.

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

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