Asparagine availability controls germinal center B cell homeostasis

Area of Science:

• Immunology
• Metabolic Biology
• Cell Biology

Background:

• Germinal center (GC) B cells undergo rapid proliferation, necessitating significant metabolic reprogramming.
• The specific metabolic pathways supporting GC B cell function remain largely uncharacterized.

Purpose of the Study:

• To investigate the metabolic requirements of GC B cells, focusing on the role of asparagine (Asn) metabolism.
• To elucidate the molecular mechanisms by which Asn supports B cell function and GC homeostasis.

Main Methods:

• Integrated metabolomic and transcriptomic profiling of GC B cells.
• Conditional deletion of asparagine synthetase (Asns) in B cells.
• Assessment of B cell function, GC reactions, and humoral responses under varying Asn conditions.

Main Results:

• Asparagine (Asn) metabolism and asparagine synthetase (ASNS) were significantly upregulated in GC B cells.
• Loss of Asns impaired B cell survival and proliferation, especially in low Asn environments.
• Asn deprivation compromised the GC reaction, affinity maturation, and antiviral humoral immunity.
• Metabolic adaptation to Asn absence relied on ASNS and impacted oxidative phosphorylation and nucleotide synthesis.

Conclusions:

• Asparagine metabolism is essential for GC B cell function and maintaining GC homeostasis.
• ASNS plays a critical role in enabling B cells to adapt to nutrient availability and support robust immune responses.