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Publication : SREBP signaling is essential for effective B cell responses.

First Author  Luo W Year  2023
Journal  Nat Immunol Volume  24
Issue  2 Pages  337-348
PubMed ID  36577930 Mgi Jnum  J:353951
Mgi Id  MGI:7495966 Doi  10.1038/s41590-022-01376-y
Citation  Luo W, et al. (2023) SREBP signaling is essential for effective B cell responses. Nat Immunol 24(2):337-348
abstractText  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.
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