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Abstract Number: 21

Reciprocal Regulation of B Cells on Bleomycin-Induced Scleroderma Model: IL-6-Producing Effector B Cells Play a Pathogenic Role, While IL-10-Producing Regulatory B Cells Play a Protective Role

Takashi Matsushita1, Yasuhito Hamaguchi1, Minoru Hasegawa2, Manabu Fujimoto3 and Kazuhiko Takehara4, 1Department of Dermatology, Kanazawa University, kanazawa, Japan, 2Department of Dermatology, University of Fukui, Fukui, Japan, 3Department of Dermatology, University of Tsukuba, Tsukuba, Japan, 4Department of Dermatology, Kanazawa University, Kanazawa, Japan

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: B cells, IL-6, regulatory cells and systemic sclerosis

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Session Information

Date: Sunday, November 5, 2017

Title: B Cell Biology and Targets in Autoimmune Disease Poster

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: IL-10-producing regulatory B (Breg) cells negatively regulate autoimmune diseases. We reported that Breg cells play a protective role in a mouse model of systemic sclerosis (SSc) and in patients. Recent studies indicate that IL-6-producing effector B (Beff) cells have pathogenic effect in autoimmune diseases. IL-6 plays a critical role for the pathogenesis of SSc, and a phase III trial of anti-IL-6R antibody (tocilizumab) is ongoing in patients with SSc. However, the phenotype and function of IL-6-producing Beff cells remains unclear. In this study, we investigated the phenotype of IL-6-producing Beff cells and their role in SSc pathogenesis.

Methods: B cell subsets were sorted and cytokine production was measured by intracellular cytokine staining. We generated mixed bone marrow chimeric mice with a B cell_specific deficiency in IL-6 or IL-10 production (B-IL-6-/- or B-IL-10-/-), together with control chimeras (B-WT). Skin fibrosis was assessed 4 weeks after the initiation of bleomycin treatment in mixed bone marrow chimeric mice.

Results: Most splenic IL-6 producing Beff cells were detected within the marginal zone (MZ) B cell subset, while IL-10-producing Breg cells were detected within the MZ B and B1 B cell subsets, but not within the follicular B cell subset (Fig 1). Serum IL-6 levels gradually increased with the development of fibrosis in bleomycin-induced scleroderma mice, while serum IL-10 levels did not. In addition, the frequency of splenic IL-6-producing Beff cells in bleomycin-treated mice was significantly increased. The bleomycin-induced skin fibrosis was attenuated in B-IL-6-/- mice compared with that in B-WT mice. In contrast, B-IL-10-/- mice showed more severe skin fibrosis than B-WT mice (Fig 2).

Conclusion: IL-6-producing Beff cells play a pathogenic role in bleomycin-induced scleroderma model, while IL-10-producing Breg cells play a protective role (Fig 3). Thus, B cells have reciprocal roles in SSc pathogenesis, presenting pathogenic and protective functions.

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Disclosure: T. Matsushita, None; Y. Hamaguchi, None; M. Hasegawa, None; M. Fujimoto, None; K. Takehara, None.

To cite this abstract in AMA style:

Matsushita T, Hamaguchi Y, Hasegawa M, Fujimoto M, Takehara K. Reciprocal Regulation of B Cells on Bleomycin-Induced Scleroderma Model: IL-6-Producing Effector B Cells Play a Pathogenic Role, While IL-10-Producing Regulatory B Cells Play a Protective Role [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/reciprocal-regulation-of-b-cells-on-bleomycin-induced-scleroderma-model-il-6-producing-effector-b-cells-play-a-pathogenic-role-while-il-10-producing-regulatory-b-cells-play-a-protective-role/. Accessed .
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