Innate and adaptive signals enhance differentiation and expansion of dual-antibody autoreactive B cells in lupus.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30266981.
- Also identified by DOI 10.1038/s41467-018-06293-z and PMC identifier 6162205.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Autoreactive B cells have a major function in autoimmunity. A small subset of B cells expressing two distinct B-cell-antigen-receptors (B<sub>2R</sub> 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 B<sub>2R</sub> cell numbers and effector function in autoimmune mice. Compared with conventional B cells, B<sub>2R</sub> 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.
Medical subject headings
- Autoantibodies
- B-Lymphocyte Subsets
- Cell Differentiation
- Cell Proliferation
- Lupus Erythematosus, Systemic
- Signal Transduction