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Author Notes:
Correspondence: jmboss@emory.edu
M.J.P. designed and performed experiments, analyzed data and wrote the manuscript.
D.G.P. performed experiments.
C.D.S. performed bioinformatic analyses.
J.M.B. designed experiments and wrote the manuscript.
All authors edited the manuscript.
The authors declare no competing interests.
Subjects:
Research Funding:
This work was supported by an NIH grant (1R01AI123733) to J.M.B.
Keywords:
- Science & Technology
- Life Sciences & Biomedicine
- Cell Biology
- TRANSCRIPTION FACTOR XBP-1
- CELL DIFFERENTIATION
- B-CELL
- AEROBIC GLYCOLYSIS
- ACTIVATION
- LYMPHOCYTES
- PHOSPHORYLATION
- MITOCHONDRIA
- EXPRESSION
- SURVIVAL
Progressive Upregulation of Oxidative Metabolism Facilitates Plasmablast Differentiation to a T-Independent Antigen
Abstract:
Transitioning from a metabolically quiescent naive B cell to an antibody-secreting plasmablast requires division-dependent cellular differentiation. Though cell division demands significant ATP and metabolites, the metabolic processes used for ATP synthesis during plasmablast formation are not well described. Here, the metabolic requirements for plasmablast formation were determined. Following T-independent stimulation with lipopolysaccharide, B cells increased expression of the oxidative phosphorylation machinery in a stepwise manner. Such activated B cells have increased capacity to perform oxidative phosphorylation but showed dependency on glycolysis. Plasmablasts displayed higher oxidative metabolism to support antibody secretion, as inhibiting oxidative ATP production resulted in decreased antibody titers. Differentiation by Blimp1 was required for this increase in oxidative metabolism, as Blimp1-deficient cells proliferate but do not upregulate oxidative phosphorylation. Together, these findings identify a shift in metabolic pathways as B cells differentiate, as well as the requirement for increased metabolic potential to support antibody production. Price et al. identify a metabolic switch in B cells that is required for maximal antibody secretion. Proliferating, activated B cells switch from glycolysis to oxidative phosphorylation as they differentiate into plasmablasts.
Copyright information:
© 2018 The Author(s)
This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).
