Regulation of humoral immune response by HIF-1α-dependent metabolic reprogramming of the germinal center reaction

Hypoxia-inducible factor-1 alpha (HIF-1 alpha) has been implicated in the regulation of many genes responsible for aerobic glycolysis; however, the role of HIF-1 alpha in B-cell metabolism has not been well defined. Here, we analyzed patterns of gene expression and oxygen consumption rates in B-cell subpopulations from humans and mice and described a model of HIF-1 alpha-mediated B-cell metabolic reprogramming during the germinal center (GC) reaction. Importantly, we found that HIF-1 alpha was highly expressed in GC B-cells, and HIF-1 alpha deficiency in B-cells impaired a functional GC reaction, resulting in defective class-switch recombination and generation of high-affinity plasma cells. These results identified an important role of HIF-1 alpha in regulating humoral immunity through metabolic reprogramming during the GC response. This newly discovered metabolic character of GC B-cells will advance our understanding of GC biology and B-cell lymphomagenesis.

Automated summary

The study reveals the crucial role of HIF-1 alpha in regulating humoral immunity through metabolic reprogramming in GC B-cells, with deficiency impairing the functional GC response and affecting the generation of high-affinity plasma cells. This newly discovered metabolic characteristic of GC B-cells will enhance understanding of GC biology and B-cell lymphomagenesis.