Asparagine availability controls germinal center B cell homeostasis.

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.

Fuelling B cells: dynamic regulation of B cell metabolism.

B cells experience extreme alterations in their metabolism throughout their life cycle, from naïve B cells, which have minimal activity, to germinal centre (GC) B cells, which proliferate at the fastest rate of all cells, to long-lived plasma cells with very high levels of protein production that can persist for decades. The underpinning of these transitions remains incompletely understood, and a key question is how utilisation of fuel source supports B cell metabolism. For example, GC B cells, unlike almost all rapidly proliferating cells, mainly use fatty acid oxidation rather than glycolysis.