Antibody-secreting cell destiny emerges during the initial stages of B-cell activation.
Christopher D ScharerDillon G PattersonTian MiMadeline J PriceSakeenah L HicksJeremy M BossPublished in: Nature communications (2020)
Upon stimulation, B cells assume heterogeneous cell fates, with only a fraction differentiating into antibody-secreting cells (ASC). Here we investigate B cell fate programming and heterogeneity during ASC differentiation using T cell-independent models. We find that maximal ASC induction requires at least eight cell divisions in vivo, with BLIMP-1 being required for differentiation at division eight. Single cell RNA-sequencing of activated B cells and construction of differentiation trajectories reveal an early cell fate bifurcation. The ASC-destined branch requires induction of IRF4, MYC-target genes, and oxidative phosphorylation, with the loss of CD62L expression serving as a potential early marker of ASC fate commitment. Meanwhile, the non-ASC branch expresses an inflammatory signature, and maintains B cell fate programming. Finally, ASC can be further subseted based on their differential responses to ER-stress, indicating multiple development branch points. Our data thus define the cell division kinetics of B cell differentiation in vivo, and identify the molecular trajectories of B cell fate and ASC formation.
Keyphrases
- cell fate
- single cell
- rna seq
- nlrp inflammasome
- cell therapy
- high throughput
- genome wide
- induced apoptosis
- depressive symptoms
- gene expression
- computed tomography
- cell death
- magnetic resonance
- magnetic resonance imaging
- machine learning
- oxidative stress
- climate change
- signaling pathway
- cell proliferation
- transcription factor
- dna methylation
- binding protein
- heart rate
- resistance training
- artificial intelligence
- data analysis
- big data
- high density
- pi k akt
- contrast enhanced