Metabolic determinants of germinal center B cell formation and responses

Victora, G. D. & Nussenzweig, M. C. Germinal centers. Annu Rev. Immunol. 30, 429–457 (2012).

Article  CAS  PubMed  Google Scholar 

Klein, U. & Dalla-Favera, R. Germinal centres: role in B-cell physiology and malignancy. Nat. Rev. Immunol. 8, 22–33 (2008).

Article  CAS  PubMed  Google Scholar 

Victora, G. D. et al. Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. Cell 143, 592–605 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jellusova, J. Metabolic control of B cell immune responses. Curr. Opin. Immunol. 63, 21–28 (2020).

Article  CAS  PubMed  Google Scholar 

Caro-Maldonado, A. et al. Metabolic reprogramming is required for antibody production that is suppressed in anergic but exaggerated in chronically BAFF-exposed B cells. J. Immunol. 192, 3626–3636 (2014).

Article  CAS  PubMed  Google Scholar 

Jayachandran, N. et al. TAPP adaptors control B cell metabolism by modulating the phosphatidylinositol 3-kinase signaling pathway: a novel regulatory circuit preventing autoimmunity. J. Immunol. 201, 406–416 (2018).

Article  CAS  PubMed  Google Scholar 

Diaz-Munoz, M. D. et al. The RNA-binding protein HuR is essential for the B cell antibody response. Nat. Immunol. 16, 415–425 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dufort, F. J. et al. Glucose-dependent de novo lipogenesis in B lymphocytes: a requirement for ATP–citrate lyase in lipopolysaccharide-induced differentiation. J. Biol. Chem. 289, 7011–7024 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cheng, J. et al. Fumarate suppresses B-cell activation and function through direct inactivation of LYN. Nat. Chem. Biol. 18, 954–962 (2022).

Article  CAS  PubMed  Google Scholar 

Cho, S. H. et al. Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system. Nature 537, 234–238 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Semenza, G. L., Roth, P. H., Fang, H. M. & Wang, G. L. Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J. Biol. Chem. 269, 23757–23763 (1994).

Article  CAS  PubMed  Google Scholar 

Jellusova, J. et al. GSK3 is a metabolic checkpoint regulator in B cells. Nat. Immunol. 18, 303–312 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sharma, R. et al. Distinct metabolic requirements regulate B cell activation and germinal center responses. Nat. Immunol. 24, 1358–1369 (2023).

Article  CAS  PubMed  Google Scholar 

Weisel, F. J. et al. Germinal center B cells selectively oxidize fatty acids for energy while conducting minimal glycolysis. Nat. Immunol. 21, 331–342 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen, D. et al. Coupled analysis of transcriptome and BCR mutations reveals role of OXPHOS in affinity maturation. Nat. Immunol. 22, 904–913 (2021).

Article  CAS  PubMed  Google Scholar 

Ducker, G. S. et al. Reversal of cytosolic one-carbon flux compensates for loss of the mitochondrial folate pathway. Cell Metab. 23, 1140–1153 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Galibert, L. et al. CD40 and B cell antigen receptor dual triggering of resting B lymphocytes turns on a partial germinal center phenotype. J. Exp. Med. 183, 77–85 (1996).

Article  CAS  PubMed  Google Scholar 

D’Avola, A. et al. PHGDH is required for germinal center formation and is a therapeutic target in MYC-driven lymphoma. J. Clin. Invest. 132, e153436 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Haniuda, K., Nojima, T. & Kitamura, D. In vitro-induced germinal center B cell culture system. Methods Mol. Biol. 1623, 125–133 (2017).

Article  CAS  PubMed  Google Scholar 

Kawai, J. et al. Structure-based design and synthesis of an isozyme-selective MTHFD2 inhibitor with a tricyclic coumarin scaffold. ACS Med. Chem. Lett. 10, 893–898 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li, G., Wu, J., Li, L. & Jiang, P. p53 deficiency induces MTHFD2 transcription to promote cell proliferation and restrain DNA damage. Proc. Natl Acad. Sci. USA 118, e2019822118 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gustafsson Sheppard, N. et al. The folate-coupled enzyme MTHFD2 is a nuclear protein and promotes cell proliferation. Sci. Rep. 5, 15029 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nojima, T. et al. In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo. Nat. Commun. 2, 465 (2011).

Article  PubMed  Google Scholar 

Zhao, R. et al. A GPR174–CCL21 module imparts sexual dimorphism to humoral immunity. Nature 577, 416–420 (2020).

Article  CAS  PubMed  Google Scholar 

Emmanuel, N. et al. Purine nucleotide availability regulates mTORC1 activity through the Rheb GTPase. Cell Rep. 19, 2665–2680 (2017).

Article  CAS  PubMed  Google Scholar 

Jiang, P., Du, W. & Wu, M. Regulation of the pentose phosphate pathway in cancer. Protein Cell 5, 592–602 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Patra, K. C. & Hay, N. The pentose phosphate pathway and cancer. Trends Biochem. Sci. 39, 347–354 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Franchina, D. G. et al. Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells. Nat. Commun. 13, 1789 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, L. W. et al. Epstein–Barr-virus-induced one-carbon metabolism drives B cell transformation. Cell Metab. 30, 539–555 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

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