@article{39d6f46c4e9a4dc7a87f03e4b68288dc,
title = "Initial B Cell Activation Induces Metabolic Reprogramming and Mitochondrial Remodeling",
abstract = "B lymphocytes provide adaptive immunity by generating antigen-specific antibodies and supporting the activation of T cells. Little is known about how global metabolism supports naive B cell activation to enable an effective immune response. By coupling RNA sequencing (RNA-seq)data with glucose isotopomer tracing, we show that stimulated B cells increase programs for oxidative phosphorylation (OXPHOS), the tricarboxylic acid (TCA)cycle, and nucleotide biosynthesis, but not glycolysis. Isotopomer tracing uncovered increases in TCA cycle intermediates with almost no contribution from glucose. Instead, glucose mainly supported the biosynthesis of ribonucleotides. Glucose restriction did not affect B cell functions, yet the inhibition of OXPHOS or glutamine restriction markedly impaired B cell growth and differentiation. Increased OXPHOS prompted studies of mitochondrial dynamics, which revealed extensive mitochondria remodeling during activation. Our results show how B cell metabolism adapts with stimulation and reveals unexpected details for carbon utilization and mitochondrial dynamics at the start of a humoral immune response.",
keywords = "Components of the Immune System, Immune Response, Immunology, Metabolomics",
author = "Waters, {Lynnea R.} and Ahsan, {Fasih M.} and Wolf, {Dane M.} and Orian Shirihai and Teitell, {Michael A.}",
note = "Funding Information: Flow cytometry was performed at the UCLA Broad Stem Cell Research Center Flow Cytometry Core. Metabolomics was performed at the UCLA Metabolomics Center by Daniel Braas. Seahorse Extracellular Flux analysis was performed at the UCLA Mitochondria and Metabolism Core by Linsey Stiles. We thank Heather Christofk for kind use of the NOVA Bioanalyzer. We thank Dr. Tara TeSlaa and Alexander J. Sercel for technical assistance and helpful discussions. Supported by the University of California Office of the President, UCLA Graduate Division (L.R.W.), and NIH grants GM007185 (L.R.W.), CA90571, CA156674, GM073981, CA185189, GM114188 (M.A.T.), and the Air Force Office of Scientific Research FA9550-15-1-0406 (M.A.T.). Conceptualization, L.R.W. F.M.A. and M.A.T.; Methodology, L.R.W. D.M.W. O.S. and F.M.A.; Formal Analysis, L.R.W. and F.M.A.; Investigation, L.R.W. F.M.A. and D.M.W; Data Curation, F.M.A. Writing – Original Draft, L.R.W; Writing – Review & Editing, L.R.W. F.M.A. and M.A.T.; Visualization, L.R.W. F.M.A. and D.M.W.; Supervision, M.A.T. and O.S.; Funding Acquisition, L.R.W. and M.A.T. The authors declare no competing interests. Funding Information: Flow cytometry was performed at the UCLA Broad Stem Cell Research Center Flow Cytometry Core. Metabolomics was performed at the UCLA Metabolomics Center by Daniel Braas. Seahorse Extracellular Flux analysis was performed at the UCLA Mitochondria and Metabolism Core by Linsey Stiles. We thank Heather Christofk for kind use of the NOVA Bioanalyzer. We thank Dr. Tara TeSlaa and Alexander J. Sercel for technical assistance and helpful discussions. Supported by the University of California Office of the President, UCLA Graduate Division (L.R.W.), and NIH grants GM007185 (L.R.W.), CA90571 , CA156674 , GM073981 , CA185189 , GM114188 (M.A.T.), and the Air Force Office of Scientific Research FA9550-15-1-0406 (M.A.T.). Publisher Copyright: {\textcopyright} 2018 The Author(s)",
year = "2018",
month = jul,
day = "27",
doi = "10.1016/j.isci.2018.07.005",
language = "English",
volume = "5",
pages = "99--109",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
}