Glucose Requirement of Antigen-Specific Autoreactive B Cells and CD4+ T Cells

Georges Abboud, Seung Chul Choi, Xiaojuan Zhang, Yuk Pheel Park, Nathalie Kanda, Leilani Zeumer-Spataro, Morgan Terrell, Xiangyu Teng, Kirsten Nündel, Mark J. Shlomchik, Laurence Morel

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The activation of lymphocytes in patients with lupus and in mouse models of the disease is coupled with an increased cellular metabolism in which glucose plays a major role. The pharmacological inhibition of glycolysis with 2-deoxy-D-glucose (2DG) reversed the expansion of follicular helper CD4+ T cells and germinal center B cells in lupus-prone mice, as well as the production of autoantibodies. The response of foreign Ags was however not affected by 2DG in these mice, suggesting that B and CD4+ T cell activation by autoantigens is uniquely sensitive to glycolysis. In this study, we tested this hypothesis with monoclonal B cells and CD4+ T cells specific for lupus-relevant autoantigens. AM14 Vk8R (AM14) transgenic B cells are activated by IgG2a/chromatin immune complexes and they can receive cognate help from chromatin-specific 13C2 CD4+ T cells. We showed that activation of AM14 B cells by their cognate Ag PL2-3 induced glycolysis, and that the inhibition of glycolysis reduced their activation and differentiation into Ab-forming cells, in the absence or presence of T cell help. The dependency of autoreactive B cells on glycolysis is in sharp contrast with the previously reported dependency of 4-hydroxy-3-nitrophenyl acetyl-specific B cells on fatty acid oxidation. Contrary to AM14 B cells, the activation and differentiation of 13C2 T cells into follicular helper CD4+ T cells was not altered by 2DG, which differs from polyclonal CD4+ T cells from lupus-prone mice. These results further define the role of glycolysis in the production of lupus autoantibodies and demonstrate the need to evaluate the metabolic requirements of Ag-specific B and T cells.

Original languageEnglish (US)
Pages (from-to)377-388
Number of pages12
JournalJournal of Immunology
Volume210
Issue number4
DOIs
StatePublished - Feb 15 2023

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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