CD11c+ B Cells Participate in the Pathogenesis of Graves' Disease by Secreting Thyroid Autoantibodies and Cytokines.

Abstract

Graves' disease (GD) is a common autoimmune disorder with an elevation in pathogenic autoantibodies, specifically anti-thyrotropin receptor antibodies (TRAbs), which are secreted by autoreactive B cells. To date, there has been little research on self-reactive B cells in GD. In the current study, we reported that a unique B-cell subset, CD11c+ B cells, was expanded in the peripheral blood (PB) of GD patients, as detected by flow cytometry. The frequency of CD11c+ B cells was positively correlated with serum TRAb levels. The flow cytometry data showed that CD11c expression was higher in a variety of B-cell subsets and that CD11c+ B cells presented a distinct immunophenotype compared to paired CD11c- B cells. Immunohistochemical and immunofluorescence staining indicated the presence of CD11c+CD19+ B cells in lymphocyte infiltration areas of the GD thyroid. Flow cytometric analysis of PB and fine-needle aspiration (FNA) samples showed that compared to PB CD11c+ B cells, CD11c+ B cells in the thyroid accumulated and further differentiated. We found that CD11c+ B cells from the PB of GD patients were induced to differentiate into autoreactive antibody-secreting cells (ASCs) capable of secreting TRAbs in vitro. Luminex liquid suspension chip detection data showed that CD11c+ B cells also secreted a variety of cytokines, including proinflammatory cytokines, anti-inflammatory cytokines, and chemokines, which might play roles in regulating the local inflammatory response and infiltration of lymphocytes in the thyroid. In addition, we performed a chemotaxis assay in a Transwell chamber to verify that CD11c+ B cells were recruited by thyroid follicular cells (TFCs) via the CXCR3-CXCL10 axis. In conclusion, our study determined that CD11c+ B cells were involved in the pathogenesis of GD in multiple ways and might represent a promising immunotherapeutic target in the future.

• Authors: Yedi Cao, Xue Zhao, Ran You, Yang Zhang, Chenxue Qu, Youyuan Huang, Yang Yu, Yan Gong, Tiechuan Cong, Enmin Zhao, Lanbo Zhang, Ying Gao, Junqing Zhang
• Journal: Frontiers in immunology (Front Immunol) Vol. 13 Pg. 836347 ( 2022) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 35386700 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Cao, Zhao, You, Zhang, Qu, Huang, Yu, Gong, Cong, Zhao, Zhang, Gao and Zhang.

Chemical References

• Autoantibodies
• Cytokines

Topics

• Autoantibodies
• B-Lymphocytes
• Cytokines (metabolism)
• Graves Disease
• Humans