Metabolic reprogramming is required for antibody production that is suppressed
in anergic but exaggerated in chronically BAFF-exposed B cells.
Authors Caro-Maldonado A, Wang R, Nichols AG, Kuraoka M, Milasta S, Sun LD, Gavin AL,
Abel ED, Kelsoe G, Green DR, Rathmell JC
Submitted By Submitted Externally on 3/4/2015
Status Published
Journal Journal of immunology (Baltimore, Md. : 1950)
Year 2014
Date Published 4/15/2014
Volume : Pages 192 : 3626 - 36
PubMed Reference 24616478
Abstract B cell activation leads to proliferation and Ab production that can protect from
pathogens or promote autoimmunity. Regulation of cell metabolism is essential to
support the demands of lymphocyte growth and effector function and may regulate
tolerance. In this study, we tested the regulation and role of glucose uptake
and metabolism in the proliferation and Ab production of control, anergic, and
autoimmune-prone B cells. Control B cells had a balanced increase in lactate
production and oxygen consumption following activation, with proportionally
increased glucose transporter Glut1 expression and mitochondrial mass upon
either LPS or BCR stimulation. This contrasted with metabolic reprogramming of T
cells, which had lower glycolytic flux when resting but disproportionately
increased this pathway upon activation. Importantly, tolerance greatly affected
B cell metabolic reprogramming. Anergic B cells remained metabolically
quiescent, with only a modest increase in glycolysis and oxygen consumption with
LPS stimulation. B cells chronically stimulated with elevated BAFF, however,
rapidly increased glycolysis and Ab production upon stimulation. Induction of
glycolysis was critical for Ab production, as glycolytic inhibition with the
pyruvate dehydrogenase kinase inhibitor dichloroacetate sharply suppressed B
cell proliferation and Ab secretion in vitro and in vivo. Furthermore, B
cell-specific deletion of Glut1 led to reduced B cell numbers and impaired Ab
production in vivo. Together, these data show that activated B cells require
Glut1-dependent metabolic reprogramming to support proliferation and Ab
production that is distinct from T cells and that this glycolytic reprogramming
is regulated in tolerance.

Investigators with authorship
E. Dale AbelUniversity of Iowa