Asparagine availability controls germinal center B cell homeostasis
Issued Date
2024-12-13
Resource Type
eISSN
24709468
Scopus ID
2-s2.0-85212629988
Pubmed ID
39671468
Journal Title
Science immunology
Volume
9
Issue
102
Rights Holder(s)
SCOPUS
Bibliographic Citation
Science immunology Vol.9 No.102 (2024) , eadl4613
Suggested Citation
Yazicioglu Y.F., Marin E., Andrew H.F., Bentkowska K., Johnstone J.C., Mitchell R., Wong Z.Y., Zec K., Fergusson J., Borsa M., Raza I.G.A., Attar M., Ali M., Kronsteiner B., Furlani I.L., MacRae J.I., Devine M.J., Coles M., Buckley C.D., Dunachie S.J., Clarke A.J. Asparagine availability controls germinal center B cell homeostasis. Science immunology Vol.9 No.102 (2024) , eadl4613. doi:10.1126/sciimmunol.adl4613 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/102562
Title
Asparagine availability controls germinal center B cell homeostasis
Corresponding Author(s)
Other Contributor(s)
Abstract
The rapid proliferation of germinal center (GC) B cells requires metabolic reprogramming to meet energy demands, yet these metabolic processes are poorly understood. By integrating metabolomic and transcriptomic profiling of GC B cells, we identified that asparagine (Asn) metabolism was highly up-regulated and essential for B cell function. Asparagine synthetase (ASNS) was up-regulated after B cell activation through the integrated stress response sensor GCN2. Conditional deletion of Asns in B cells impaired survival and proliferation in low Asn conditions. Removal of environmental Asn by asparaginase or dietary restriction compromised the GC reaction, impairing affinity maturation and the humoral response to influenza infection. Furthermore, metabolic adaptation to the absence of Asn required ASNS, and oxidative phosphorylation, mitochondrial homeostasis, and synthesis of nucleotides were particularly sensitive to Asn deprivation. These findings demonstrate that Asn metabolism acts as a key regulator of B cell function and GC homeostasis.