Fuelling B cells: dynamic regulation of B cell metabolism

Johnstone, Julia C.; Yazicioglu, Yavuz F.; Clarke, Alexander J.

doi:10.1016/j.coi.2024.102484

Current Opinion in Immunology

2024

DOI: 10.1016/j.coi.2024.102484

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Fuelling B cells: dynamic regulation of B cell metabolism

Julia C. Johnstone,

Yavuz F. Yazicioglu,

Alexander J. Clarke

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2024

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References 67 publications

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LPS stimulates dynamic changes in B cell metabolism to promote proliferation

Cheung,

Razsolkov,

Bonacina

et al. 2024

Preprint

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Following activation, naive 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, neutral 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. LPS stimulation increased cellular cholesterol levels and inhibition of the rate-limiting enzymes HMG-CoA-reductase (HMGCR) and Squalene monooxygenase in the cholesterol biosynthesis pathway significantly reduced proliferation. The critical role of the cholesterol biosynthetic pathway was not limited to LPS. Stimulation via TLR7, TLR9, CD40 or 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.

show abstract

LPS stimulates dynamic changes in B cell metabolism to promote proliferation

Cheung,

Razsolkov,

Bonacina

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

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Fuelling B cells: dynamic regulation of B cell metabolism

Cited by 1 publication

References 67 publications

LPS stimulates dynamic changes in B cell metabolism to promote proliferation

LPS stimulates dynamic changes in B cell metabolism to promote proliferation

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