Antibody-secreting cell destiny emerges during the initial stages of B-cell activation

Christopher D. Scharer, Dillon G. Patterson, Tian Mi, Madeline J. Price, Sakeenah L. Hicks and Jeremy M. Boss ()
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Christopher D. Scharer: Emory University School of Medicine
Dillon G. Patterson: Emory University School of Medicine
Tian Mi: Emory University School of Medicine
Madeline J. Price: Emory University School of Medicine
Sakeenah L. Hicks: Emory University School of Medicine
Jeremy M. Boss: Emory University School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-14

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.

Date: 2020
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DOI: 10.1038/s41467-020-17798-x

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