SREBP signaling is essential for effective B cell responses

Wei Luo, Julia Z. Adamska, Chunfeng Li, Rohit Verma, Qing Liu, Thomas Hagan, Florian Wimmers, Shakti Gupta, Yupeng Feng, Wenxia Jiang, Jiehao Zhou, Erika Valore, Yanli Wang, Meera Trisal, Shankar Subramaniam, Timothy F. Osborne, Bali Pulendran

Research output: Contribution to journalArticlepeer-review

Abstract

Our previous study using systems vaccinology identified an association between the sterol regulatory binding protein (SREBP) pathway and humoral immune response to vaccination in humans. To investigate the role of SREBP signaling in modulating immune responses, we generated mice with B cell- or CD11c+ antigen-presenting cell (APC)-specific deletion of SCAP, an essential regulator of SREBP signaling. Ablation of SCAP in CD11c+ APCs had no effect on immune responses. In contrast, SREBP signaling in B cells was critical for antibody responses, as well as the generation of germinal centers,memory B cells and bone marrow plasma cells. SREBP signaling was required for metabolic reprogramming in activated B cells. Upon mitogen stimulation, SCAP-deficient B cells could not proliferate and had decreased lipid rafts. Deletion of SCAP in germinal center B cells using AID-Cre decreased lipid raft content and cell cycle progression. These studies provide mechanistic insights coupling sterol metabolism with the quality and longevity of humoral immunity.

Original languageEnglish (US)
Pages (from-to)337-348
Number of pages12
JournalNature Immunology
Volume24
Issue number2
DOIs
StatePublished - Feb 2023

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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