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Lipopolysaccharide stimulates dynamic changes in B cell metabolism to promote cell proliferation - naive and LPS data

ABSTRACT: Following activation, naïve B cells exit quiescence and enter a proliferative phase before becoming mature antibody-producing or memory B cells. One method of activation is to use Lipopolysaccharide (LPS), a well-established B cell mitogen that can drive proliferation ex vivo. Using quantitative proteomics, we identify an upregulation of proteins following LPS stimulation involved in metabolic pathways including amino acid uptake and cholesterol biosynthesis. We highlight the large amino acid transporter SLC7A5 as a target of LPS-induced activation, and by utilising SLC7A5 conditional knockout mice, we demonstrate the requirement of this transporter for B cell proliferation ex vivo. Inhibition of the rate-limiting enzymes HMG-CoA-reductase (HMGCR) and Squalene monooxygenase in the cholesterol biosynthesis pathway significantly reduced proliferation. The role of the cholesterol biosynthetic pathway was not limited to LPS. Stimulation via TLR7, TLR9, CD40 and the B Cell Receptor also increased cholesterol levels and inhibition of HMGCR reduced proliferation. Together these results suggest a common requirement for metabolic rewiring in B cells to allow proliferation in response to activation.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): B Cell, Lymph Node

SUBMITTER: Andrew Howden

LAB HEAD: Professor Simon

PROVIDER: PXD057739 | Pride | 2026-05-18

REPOSITORIES: Pride

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			Action	DRS
	AH-LP3-R1.raw	Raw
	AH-LP3-R2.raw	Raw
	AH-LP3-R3.raw	Raw
	AH-LP3-R4.raw	Raw
	Naive_BR1.raw	Raw

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Project description: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.

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