Fatty acid metabolism and dietary lipid composition shape B-cell responses
- 1Centre de Recherche de l'ôHpital Maisonneuve-Rosemont, Montreal, Canada, Department of Obstetrics-Gynecology, Department of Biomedical Sciences, Université de M
Abstract
B-cell activation requires extensive metabolic reprogramming, yet how B cells acquire and utilize extracellular fatty acids and adapt to changes in lipid availability remains poorly understood. Here, we show that B-cell activation and the extracellular lipid environment dynamically regulate B cells. B-cell receptor (BCR) and Toll-like receptor 4 (TLR4) stimulation induced distinct mitochondrial and lipid-handling programs, differentially regulating fatty-acid uptake, cholesterol acquisition, lipid storage and mitochondrial respiration. Disrupting long-chain fatty-acid uptake, acyl-CoA activation, or mitochondrial utilisation impaired B-cell proliferation, demonstrating that multiple steps of fatty-acid metabolism are required for B-cell expansion. However, increasing extracellular fatty-acid availability alone did not enhance proliferation, indicating that fatty-acid acquisition and metabolic utilisation are functionally distinct. B cells also acquired fatty acids directly from adipocytes, identifying the local microenvironment as a potential source of metabolic substrates. In vivo, dietary fatty-acid chain length differentially shaped the germinal-centre response. A long-chain fatty-acid-rich diet increased germinal-centre B cells and T follicular helper cells and induced mitochondrial and transcriptional changes that partially converged with those observed following obesogenic feeding. Circulating lipidomics further revealed shared remodelling of lipid species between long-chain fatty-acid-rich and obesogenic diets, including altered partitioning of stearate-containing lipids. Exogenous fatty acids also modified membrane order in activated B cells, suggesting that lipid availability can influence both metabolic and biophysical properties. Together, these findings establish fatty-acid uptake, activation, and utilization as integral components of B-cell metabolic adaptation and demonstrate that dietary fatty-acid composition can remodel the lipid environment and germinal-centre response.
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BibTeX
@misc{ngwenyama2026fatty,
title = {{Fatty acid metabolism and dietary lipid composition shape B-cell responses}},
author = {B. B. Ngwenyama and L. Bourguignon and E. B. Gianneli and Y. Benazzouk and M. Laflamme and I. Giacomini and T. K. Nguyen and C. Viau and A. L. Collin and F. Zani and J. Blagih},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.02.756283},
url = {https://www.biorxiv.org/content/10.64898/2026.10.02.756283v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Fatty acid metabolism and dietary lipid composition shape B-cell responses
AU - B. B. Ngwenyama
AU - L. Bourguignon
AU - E. B. Gianneli
AU - Y. Benazzouk
AU - M. Laflamme
AU - I. Giacomini
AU - T. K. Nguyen
AU - C. Viau
AU - A. L. Collin
AU - F. Zani
AU - J. Blagih
PY - 2026
DA - 2026/10/02
PB - bioRxiv
DO - 10.64898/2026.10.02.756283
UR - https://www.biorxiv.org/content/10.64898/2026.10.02.756283v1
AB - B-cell activation requires extensive metabolic reprogramming, yet how B cells acquire and utilize extracellular fatty acids and adapt to changes in lipid availability remains poorly understood. Here, we show that B-cell activation and the extracellular lipid environment dynamically regulate B cells. B-cell receptor (BCR) and Toll-like receptor 4 (TLR4) stimulation induced distinct mitochondrial and lipid-handling programs, differentially regulating fatty-acid uptake, cholesterol acquisition, lipid storage and mitochondrial respiration. Disrupting long-chain fatty-acid uptake, acyl-CoA activation, or mitochondrial utilisation impaired B-cell proliferation, demonstrating that multiple steps of fatty-acid metabolism are required for B-cell expansion. However, increasing extracellular fatty-acid availability alone did not enhance proliferation, indicating that fatty-acid acquisition and metabolic utilisation are functionally distinct. B cells also acquired fatty acids directly from adipocytes, identifying the local microenvironment as a potential source of metabolic substrates. In vivo, dietary fatty-acid chain length differentially shaped the germinal-centre response. A long-chain fatty-acid-rich diet increased germinal-centre B cells and T follicular helper cells and induced mitochondrial and transcriptional changes that partially converged with those observed following obesogenic feeding. Circulating lipidomics further revealed shared remodelling of lipid species between long-chain fatty-acid-rich and obesogenic diets, including altered partitioning of stearate-containing lipids. Exogenous fatty acids also modified membrane order in activated B cells, suggesting that lipid availability can influence both metabolic and biophysical properties. Together, these findings establish fatty-acid uptake, activation, and utilization as integral components of B-cell metabolic adaptation and demonstrate that dietary fatty-acid composition can remodel the lipid environment and germinal-centre response.
ER -