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Nat Commun. 2018 Sep 28;9(1):3973. doi: 10.1038/s41467-018-06293-z.

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

Author information

1
Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.
2
Center for Genes, Environment and Health, National Jewish Health, Denver, CO, 80206, USA.
3
Inflammation and Immunology, Pfizer Research, Cambridge, MA, 02140, USA.
4
Immuno-Oncology Discovery, FivePrime Therapeutics, South San Francisco, CA, 94080, USA.
5
Department of Biomedical Research, National Jewish Health, Denver, CO, 80206, USA.
6
Department of Pediatrics, National Jewish Health, Denver, CO, 80206, USA.
7
Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO, 80045, USA. Roberta.Pelanda@ucdenver.edu.
8
Department of Biomedical Research, National Jewish Health, Denver, CO, 80206, USA. Roberta.Pelanda@ucdenver.edu.

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.

PMID:
30266981
PMCID:
PMC6162205
DOI:
10.1038/s41467-018-06293-z
[Indexed for MEDLINE]
Free PMC Article

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