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

Cellular & Molecular Immunology volume 16, pages 367–379 (2019)Cite this article

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.

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Fig. 1: Plasma from SLE patients protects transitional B cells from apoptosis.
Fig. 2: SLE plasma enhances Btr cells survival in a type I IFN-dependent manner.
Fig. 3: IFN-α protects Btr cells from spontaneous apoptosis.
Fig. 4: NF-κB pathway is involved in IFN-α-mediated Btr cell survival.
Fig. 5: Proinflammatory potency of transitional B cells in active SLE patients.
Fig. 6: IFN-α promotes IL-6 expression in transitional B cells.
Fig. 7: The frequency of IL-6-producing Btr cells is strongly correlated with disease activities in SLE patients.
Fig. 8: The frequency of IL-6-producing Btr cells is decreased in SLE patients after short standard therapy.

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Acknowledgements

This work was supported by the National Basic Research Program of China (No. 2014CB541904); the National Natural Science Foundation of China (Nos. 31470879 81571575 8171101311 and 31770960); the Interdisciplinary Innovation Team, External Cooperation Program (No. GJHZ201312) and Key Project QYZDB-SSW-SMC036; and the Strategic Priority Research Program (No. XDPB0303), Chinese Academy of Sciences.

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  1. These authors contributed equally: Mei Liu, Qiang Guo.

Authors and Affiliations

  1. Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences/University of Chinese Academy of Sciences, Shanghai, 200031, China

    Mei Liu, Delphine Sterlin, Shyamal Goswami, Ying Zhang, Teng Li & Xiaoming Zhang

  2. Department of Rheumatology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200001, China

    Qiang Guo, Chunmei Wu, Chunde Bao, Nan Shen & Qiong Fu

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Liu, M., Guo, Q., Wu, C. et al. Type I interferons promote the survival and proinflammatory properties of transitional B cells in systemic lupus erythematosus patients. Cell Mol Immunol 16, 367–379 (2019). https://doi.org/10.1038/s41423-018-0010-6

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