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B cells

B is for ‘Big Mac’: GCs crave a high-fat diet

Nature Immunology volume 21, pages 249–250 (2020)Cite this article

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Highly proliferative cells have classically been thought to rely on anaerobic glycolysis for fuel. Weisel et al. show that germinal center B cells break this rule, as they primarily utilize fatty acid oxidation to meet their metabolic demands.

Over the course of the immune response to most infections and immunizations, serum antibody affinity increases as a result of the Darwinian process of somatic hypermutation (SHM) of immunoglobulin genes followed by selective expansion of B cell variants bearing affinity-increasing mutations. This iterative process takes place within germinal centers (GCs), microanatomical structures that form within secondary lymphoid organs upon antigenic stimulation1. To be efficient, GC selection must be coupled to the rapid proliferation of cells bearing improved immunoglobulins. Accordingly, GC B cells are thought to be among the fastest proliferating mammalian cell types, dividing as frequently as three to five times per day2,3. In its more extreme versions, this rapid proliferation can lead to clonal bursts, in which a single positively selected B cell can take over an entire 2,000-cell-strong GC in a matter of a few days4. Although it is clear that rapid proliferation is key to affinity maturation, little is known about how GC B cells fulfill the metabolic demands required to fuel this process. In this issue of Nature Immunology, Weisel et al. show that the usual association between rapid proliferation and anaerobic glycolysis is broken in GC B cells, which instead rely primarily on fatty acid oxidation (FAO) to fuel their proliferative spurts5.

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Fig. 1: Bioenergetics of germinal center B cells.

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Authors and Affiliations

  1. Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, NY, USA

    Juhee Pae & Gabriel D. Victora

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  1. Juhee Pae
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  2. Gabriel D. Victora
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Correspondence to Gabriel D. Victora.

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The authors declare no competing interests.

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Pae, J., Victora, G.D. B is for ‘Big Mac’: GCs crave a high-fat diet. Nat Immunol 21, 249–250 (2020). https://doi.org/10.1038/s41590-020-0614-8

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  • DOI: https://doi.org/10.1038/s41590-020-0614-8

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