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- W3048004273 abstract "Abstract 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." @default.
- W3048004273 created "2020-08-13" @default.
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- W3048004273 date "2020-08-10" @default.
- W3048004273 modified "2023-10-02" @default.
- W3048004273 title "Antibody-secreting cell destiny emerges during the initial stages of B-cell activation" @default.
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- W3048004273 doi "https://doi.org/10.1038/s41467-020-17798-x" @default.
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