Initial B Cell Activation Induces Metabolic Reprogramming and Mitochondrial Remodeling

Lynnea R. Waters, Fasih M. Ahsan, Dane M. Wolf, Orian Shirihai, Michael A. Teitell

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

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.

Original languageEnglish
Pages (from-to)99-109
Number of pages11
JournaliScience
Volume5
DOIs
StatePublished - 27 Jul 2018
Externally publishedYes

Keywords

  • Components of the Immune System
  • Immune Response
  • Immunology
  • Metabolomics

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Initial B Cell Activation Induces Metabolic Reprogramming and Mitochondrial Remodeling'. Together they form a unique fingerprint.

Cite this