Progressive Upregulation of Oxidative Metabolism Facilitates Plasmablast Differentiation to a T-Independent Antigen

• Type of Material: Article
• Authors: Madeline J. Price, Emory University; Dillon G. Patterson, Emory University; Christopher Scharer, Emory University; Jeremy Boss, Emory University
• Language: English
• Date: 2018-06-12
• Publisher: Elsevier (Cell Press): OAJ
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 The Author(s)
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.celrep.2018.05.053
• Title of Journal or Parent Work: Cell Reports
• ISSN: 2211-1247
• Volume: 23
• Issue: 11
• Start Page: 3152
• End Page: 3159
• Grant/Funding Information: This work was supported by an NIH grant (1R01AI123733) to J.M.B.
• Keywords: Life Sciences & Biomedicine; TRANSCRIPTION FACTOR XBP-1; SURVIVAL; AEROBIC GLYCOLYSIS; Science & Technology; B-CELL; CELL DIFFERENTIATION; PHOSPHORYLATION; MITOCHONDRIA; EXPRESSION; LYMPHOCYTES; Cell Biology; ACTIVATION
• Research Categories: Health Sciences, Immunology; Biology, Microbiology

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.