CD28 Regulates Metabolic Fitness for Long-Lived Plasma Cell Survival.
Cell Rep
; 31(12): 107815, 2020 06 23.
Article
in En
| MEDLINE
| ID: mdl-32579940
ABSTRACT
Durable humoral immunity against epidemic infectious disease requires the survival of long-lived plasma cells (LLPCs). LLPC longevity is dependent on metabolic programs distinct from short-lived plasma cells (SLPCs); however, the mechanistic basis for this difference is unclear. We have previously shown that CD28, the prototypic T cell costimulatory receptor, is expressed on both LLPCs and SLPCs but is essential only for LLPC survival. Here we show that CD28 transduces pro-survival signaling specifically in LLPCs through differential SLP76 expression. CD28 signaling in LLPCs increased glucose uptake, mitochondrial mass/respiration, and reactive oxygen species (ROS) production. Unexpectedly, CD28-mediated regulation of mitochondrial respiration, NF-κB activation, and survival was ROS dependent. IRF4, a target of NF-κB, was upregulated by CD28 activation in LLPCs and decreased IRF4 levels correlated with decreased glucose uptake, mitochondrial mass, ROS, and CD28-mediated survival. Altogether, these data demonstrate that CD28 signaling induces a ROS-dependent metabolic program required for LLPC survival.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Plasma Cells
/
CD28 Antigens
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Cell Rep
Year:
2020
Document type:
Article
Affiliation country:
United States