Oncotarget

Research Papers: Immunology:

B cells regulate thymic CD8+T cell differentiation in lupus-prone mice

Chen Xing, Gaizhi Zhu, He Xiao, Ying Fang, Xiaoling Liu, Gencheng Han, Guojiang Chen, Chunmei Hou, Beifen Shen, Yan Li, Ning Ma and Renxi Wang _

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Oncotarget. 2017; 8:89486-89499. https://doi.org/10.18632/oncotarget.19002

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Abstract

Chen Xing1,5,*, Gaizhi Zhu1,2,*, He Xiao1,*, Ying Fang1,3, Xiaoling Liu1,4, Gencheng Han1, Guojiang Chen1, Chunmei Hou1, Beifen Shen1, Yan Li1, Ning Ma3 and Renxi Wang1

1 Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China

2 Laboratory of Cellular and Molecular Immunology, Henan University, Kaifeng, Henan, China

3 Department of Rheumatology, First hospital of Jilin University, Changchun, China

4 Department of Nephrology, The 307th Hospital of Chinese People’s Liberation Army, Beijing, China

5 Department of Stress Medicine, Beijing Institute of Basic Medical Sciences, Beijing, China

* These authors have contributed equally to this work

Correspondence to:

Renxi Wang, email:

Ning Ma, email:

Keywords: B cells, thymic CD8+T cells, RORγt, IgG, lupus-prone mice, Immunology and Microbiology Section, Immune response, Immunity

Received: February 17, 2017 Accepted: June 18, 2017 Published: July 05, 2017

Abstract

Previous studies have shown that under normal physiological conditions thymic B cells play a critical function in T cell negative selection. We tested the effect of thymic B cells on thymic T-cell differentiation in autoimmune diseases including systemic lupus erythematosus (SLE). We found that thymic B cells and CD8- CD4+ and CD4-CD8+T cells increased, whereas CD4+CD8+T cells decreased in lupus-prone mice. Once B cells were reduced, the change was reversed. Furthermore, we found that B cells blocked thymic immature single positive (ISP) CD4-CD8+CD3lo/-RORγt- T cells progression into CD4+CD8+T cells. Interestingly, we found a novel population of thymic immature T cells (CD4-CD8+CD3loRORγt+) that were induced into mature CD4-CD8+CD3+RORγt+T cells by B cells in lupus-prone mice. Importantly, we found that IgG, produced by thymic B cells, played a critical role in the differentiation of thymic CD8+ISP and mature RORγt+CD8+ T cells in lupus-prone mice. In conclusion, B cells blocked the differentiation from thymic CD8+ISP and induced the differentiation of a novel immature CD4-CD8+CD3loRORγt+T cells into mature RORγt+CD8+ T cells by secreting IgG antibody in lupus-prone mice.


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