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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Christopher D. Scharer & Dillon G. Patterson & Tian Mi & Madeline J. Price & Sakeenah L. Hicks & Jeremy M. Boss, 2020. "Antibody-secreting cell destiny emerges during the initial stages of B-cell activation," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17798-x
    DOI: 10.1038/s41467-020-17798-x
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    Cited by:

    1. Rene Yu-Hong Cheng & Joseph de Rutte & Cade Ellis K. Ito & Andee R. Ott & Lucie Bosler & Wei-Ying Kuo & Jesse Liang & Brian E. Hall & David J. Rawlings & Dino Di Carlo & Richard G. James, 2023. "SEC-seq: association of molecular signatures with antibody secretion in thousands of single human plasma cells," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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