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SREBP signaling is essential for effective B cell responses

Nature immunology, 2023-02, Vol.24 (2), p.337-348 [Peer Reviewed Journal]

2022. The Author(s), under exclusive licence to Springer Nature America, Inc. ;The Author(s), under exclusive licence to Springer Nature America, Inc. 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. ;ISSN: 1529-2908 ;EISSN: 1529-2916 ;DOI: 10.1038/s41590-022-01376-y ;PMID: 36577930

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Title:
SREBP signaling is essential for effective B cell responses
Author: Luo, Wei ; Adamska, Julia Z ; Li, Chunfeng ; Verma, Rohit ; Liu, Qing ; Hagan, Thomas ; Wimmers, Florian ; Gupta, Shakti ; Feng, Yupeng ; Jiang, Wenxia ; Zhou, Jiehao ; Valore, Erika ; Wang, Yanli ; Trisal, Meera ; Subramaniam, Shankar ; Osborne, Timothy F ; Pulendran, Bali
Subjects: Animals ; Antigen-presenting cells ; Bone marrow ; Carrier Proteins ; CD11c antigen ; CD8 antigen ; Cell activation ; Cell cycle ; Clonal deletion ; Germinal centers ; Humans ; Humoral immunity ; Immune response (humoral) ; Immunological memory ; Intracellular Signaling Peptides and Proteins - metabolism ; Lipid rafts ; Lymphocytes B ; Lymphocytes T ; Lymphoma, B-Cell - metabolism ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Memory cells ; Metabolic rate ; Metabolism ; Mice ; Plasma cells ; Sterol Regulatory Element Binding Protein 1 - metabolism ; Sterol regulatory element-binding protein ; Sterols ; Sterols - metabolism ; Vaccination
Is Part Of: Nature immunology, 2023-02, Vol.24 (2), p.337-348
Description: 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.
Publisher: United States: Nature Publishing Group
Language: English
Identifier: ISSN: 1529-2908
EISSN: 1529-2916
DOI: 10.1038/s41590-022-01376-y
PMID: 36577930
Source: AUTh Library subscriptions: ProQuest Central
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SREBP signaling is essential for effective B cell responses

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