The fat and the furious: fatty acids fuel hyperproliferative germinal center B cells

The germinal center (GC) reaction is considered the cornerstone of our humoral immune response. Localized in specialized follicles inside secondary lymphoid organs, germinal center B cells

(GCBCs) execute a pivotal task. Following an infection, the number of GCBCs is rapidly expanded, and subsequently GCBCs differentiate into specialized antibody-secreting factories. This

intricate process is driven by the positive selection of GCBCs via the B-cell receptor with the highest affinity for the respective antigen. During this period of extensive proliferation,

GCBCs are among the fastest dividing cells in our body. It has been established that cell proliferation requires tremendous amounts of energy and building blocks. However, there remains a

paucity of evidence to explain how proliferating GCBCs meet these metabolic demands. In their latest publication in Nature Immunology, Weisel et al. provided new insights that may have a

far-reaching impact on the evolution of the immunometabolism field.1

The current dogma states that proliferative cells predominantly employ (an)aerobic glycolysis.2 In this process, cells catabolize glucose into indispensable nucleotides and proteins, whilst

producing limited amounts of energy. Because glycolysis does not require oxygen and the GC was recently shown to be hypoxic,3 GCBCs are thought to display a glycolysis-dependent phenotype.

However, experiments with freshly isolated GCBCs have been technically challenging. Weisel et al. have overcome these limitations by utilizing an untouched bead-based purification approach.

The validity of their approach was confirmed by the consistently observed phenotypic and transcriptomic characteristics of bona fide ex vivo GCBCs (Extended Data Figs. 1–3).

The authors acknowledge funding support by the European Research Council (Consolidator Grant 724281 to A.B.v.S.) and Sjoerd van Deventer and Vera Dunlock for critically reading the

manuscript. The authors have no competing interest.

Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, Nijmegen, The Netherlands

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