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Innate and adaptive signals enhance differentiation and expansion of dual-antibody autoreactive B cells in lupus

Author

Listed:
  • Allison Sang

    (University of Colorado School of Medicine)

  • Thomas Danhorn

    (National Jewish Health)

  • Jacob N. Peterson

    (University of Colorado School of Medicine)

  • Andrew L. Rankin

    (Pfizer Research
    FivePrime Therapeutics)

  • Brian P. O’Connor

    (University of Colorado School of Medicine
    National Jewish Health
    National Jewish Health
    National Jewish Health)

  • Sonia M. Leach

    (National Jewish Health
    National Jewish Health)

  • Raul M. Torres

    (University of Colorado School of Medicine
    National Jewish Health)

  • Roberta Pelanda

    (University of Colorado School of Medicine
    National Jewish Health)

Abstract

Autoreactive B cells have a major function in autoimmunity. A small subset of B cells expressing two distinct B-cell-antigen-receptors (B2R cells) is elevated in many patients with systematic lupus erythematosus (SLE) and in the MRL(/lpr) mouse model of lupus, and is often autoreactive. Here we show, using RNAseq and in vitro and in vivo analyses, signals that are required for promoting B2R cell numbers and effector function in autoimmune mice. Compared with conventional B cells, B2R cells are more responsive to Toll-like receptor 7/9 and type I/II interferon treatment, display higher levels of MHCII and co-receptors, and depend on IL-21 for their homeostasis; moreover they expand better upon T cell-dependent antigen stimulation, and mount a more robust memory response, which are characteristics essential for enhanced (auto)immune responses. Our findings thus provide insights on the stimuli for the expansion of an autoreactive B cell subset that may contribute to the etiology of SLE.

Suggested Citation

  • Allison Sang & Thomas Danhorn & Jacob N. Peterson & Andrew L. Rankin & Brian P. O’Connor & Sonia M. Leach & Raul M. Torres & Roberta Pelanda, 2018. "Innate and adaptive signals enhance differentiation and expansion of dual-antibody autoreactive B cells in lupus," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06293-z
    DOI: 10.1038/s41467-018-06293-z
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