Type I interferons promote the survival and proinflammatory properties of transitional B cells in systemic lupus erythematosus patients.

Abstract

A hallmark of systemic lupus erythematosus (SLE) is the breaking of B-cell tolerance with the generation of high-affinity autoantibodies; however, the antibody-independent features of the B-cell compartment in SLE are less understood. In this study, we performed an extensive examination of B-cell subsets and their proinflammatory properties in a Chinese cohort of new-onset SLE patients. We observed that SLE patients exhibited an increased frequency of transitional B cells compared with healthy donors and rheumatoid arthritis patients. Plasma from SLE patients potently promoted the survival of transitional B cells in a type I IFN-dependent manner, which can be recapitulated by direct IFN-α treatment. Furthermore, the effect of IFN-α on enhanced survival of transitional B cells was associated with NF-κB pathway activation and reduced expression of the pro-apoptotic molecule Bax. Transitional B cells from SLE patients harbored a higher capacity to produce proinflammatory cytokine IL-6, which was also linked to the overactivated type I IFN pathway. In addition, the frequency of IL-6-producing transitional B cells was positively correlated with disease activity in SLE patients, and these cells were significantly reduced after short-term standard therapies. Thus, the current study provides a direct link between type I IFN pathway overactivation and the abnormally high frequency and proinflammatory properties of transitional B cells in active SLE patients, which contributes to the understanding of the roles of type I IFNs and B cells in the pathogenesis of SLE.

• Authors: Mei Liu, Qiang Guo, Chunmei Wu, Delphine Sterlin, Shyamal Goswami, Ying Zhang, Teng Li, Chunde Bao, Nan Shen, Qiong Fu, Xiaoming Zhang
• Journal: Cellular & molecular immunology (Cell Mol Immunol) Vol. 16 Issue 4 Pg. 367-379 (04 2019) ISSN: 2042-0226 [Electronic] China
• PMID: 29563616 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• BAX protein, human
• Interferon-alpha
• Interleukin-6
• NF-kappa B
• bcl-2-Associated X Protein

Topics

• Adolescent
• Adult
• Aged
• Apoptosis (drug effects, immunology)
• Arthritis, Rheumatoid (blood, immunology)
• Autoantibodies (blood)
• B-Lymphocyte Subsets (drug effects, immunology, metabolism)
• Cell Survival (drug effects, immunology)
• Cells, Cultured
• China
• Cohort Studies
• Female
• Humans
• Inflammation (immunology, metabolism)
• Interferon-alpha (pharmacology)
• Interleukin-6 (metabolism)
• Leukocytes, Mononuclear (metabolism)
• Lupus Erythematosus, Systemic (blood, immunology, physiopathology, therapy)
• Male
• Middle Aged
• NF-kappa B (metabolism)
• Signal Transduction (drug effects, immunology)
• bcl-2-Associated X Protein (metabolism)