Conserved Epigenetic Programming and Enhanced Heme Metabolism Drive Memory B Cell Reactivation.
Madeline J PriceChristopher D ScharerAnna K KaniaTroy D RandallJeremy M BossPublished in: Journal of immunology (Baltimore, Md. : 1950) (2021)
Memory B cells (MBCs) have enhanced capabilities to differentiate to plasma cells and generate a rapid burst of Abs upon secondary stimulation. To determine if MBCs harbor an epigenetic landscape that contributes to increased differentiation potential, we derived the chromatin accessibility and transcriptomes of influenza-specific IgM and IgG MBCs compared with naive cells. MBCs possessed an accessible chromatin architecture surrounding plasma cell-specific genes, as well as altered expression of transcription factors and genes encoding cell cycle, chemotaxis, and signal transduction processes. Intriguingly, this MBC signature was conserved between humans and mice. MBCs of both species possessed a heightened heme signature compared with naive cells. Differentiation in the presence of hemin enhanced oxidative phosphorylation metabolism and MBC differentiation into Ab-secreting plasma cells. Thus, these data define conserved MBC transcriptional and epigenetic signatures that include a central role for heme and multiple other pathways in augmenting MBC reactivation potential.
Keyphrases
- transcription factor
- induced apoptosis
- gene expression
- cell cycle arrest
- cell cycle
- genome wide
- dna methylation
- single cell
- endoplasmic reticulum stress
- cell death
- stem cells
- dna damage
- metabolic syndrome
- cell proliferation
- hiv infected
- poor prognosis
- risk assessment
- mesenchymal stem cells
- high frequency
- electronic health record
- insulin resistance
- big data
- high fat diet induced
- genetic diversity
- loop mediated isothermal amplification