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Lipopolysaccharide stimulates dynamic changes in B cell metabolism to promote proliferation - Fluvastatin data

ABSTRACT: Naïve B cells exit quiescence and enter a proliferative state upon activation, ultimately differentiating into antibody-secreting or memory B cells. Toll-like receptor (TLR) ligands, such as lipopolysaccharide (LPS), can serve as physiological stimuli to initiate this transition. Using quantitative proteomics, we show that TLR4 engagement induces metabolic reprogramming in murine B cells, increasing the expression of amino acid transporters and cholesterol biosynthetic enzymes. The amino acid transporter SLC7A5 is markedly upregulated following LPS stimulation, and conditional deletion of Slc7a5 impairs B cell proliferation, underscoring its essential role in B cell activation. LPS also elevates intracellular cholesterol levels, and inhibition of the rate-limiting enzyme HMG-CoA reductase blocks proliferation. This effect was mediated by a dual requirement for cholesterol metabolism and protein prenylation downstream of HMG-CoA reductase. Notably, this was not unique to TLR4 signalling but is also observed in B cells activated via TLR7, TLR9, CD40, or the B cell receptor. Together, these findings reveal that metabolic rewiring, including amino acid uptake and cholesterol metabolism, is an essential feature of B cell activation and proliferation.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Spleen, B Cell

SUBMITTER: Andrew Howden

LAB HEAD: Professor Simon Arthur

PROVIDER: PXD074568 | Pride | 2026-05-18

REPOSITORIES: Pride

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			Action	DRS
	20251022_204804_Dana_Oct_2025_Report.csv	Csv
	20251022_204804_Dana_Oct_2025_Report.setup.txt	Txt
	250_2025_DUN_SA-Fluv-delip-1.raw	Raw
	250_2025_DUN_SA-Fluv-delip-2.raw	Raw
	250_2025_DUN_SA-Fluv-delip-3-Rep.raw	Raw

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