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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Allison Sang, Thomas Danhorn, Jacob N. Peterson, Andrew L. Rankin, Brian P. O’Connor, Sonia M. Leach, Raul M. Torres, Roberta Pelanda

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. More... »

PAGES

3973

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-018-06293-z

DOI

http://dx.doi.org/10.1038/s41467-018-06293-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1107235063

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30266981


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