Enhancement of T Follicular Helper Cell-Mediated Humoral Immunity Reponses During Development of Experimental Autoimmune Myasthenia Gravis.
10.1007/s12264-019-00344-1
- Author:
Ying-Zhe CUI
1
;
Si-Ying QU
1
;
Lu-Lu CHANG
1
;
Jia-Rui ZHAO
1
;
Lili MU
1
;
Bo SUN
1
;
Hu-Lun LI
1
;
Tong-Shuai ZHANG
1
;
Guang-You WANG
2
;
Qing-Fei KONG
3
Author Information
1. Department of Neurobiology, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin Medical University, Harbin, 150081, China.
2. Department of Neurobiology, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin Medical University, Harbin, 150081, China. guangyouwang@163.com.
3. Department of Neurobiology, Heilongjiang Provincial Key Laboratory of Neurobiology, Harbin Medical University, Harbin, 150081, China. kqfangel@hrbmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Acetylcholine receptor;
Experimental autoimmune myasthenia gravis;
Follicular helper T cells;
Germinal center
- MeSH:
Animals;
B-Lymphocytes;
immunology;
Disease Models, Animal;
Female;
Immunity, Humoral;
Lymph Nodes;
immunology;
Myasthenia Gravis, Autoimmune, Experimental;
immunology;
Protein Subunits;
immunology;
Proto-Oncogene Proteins c-bcl-6;
immunology;
Rats, Inbred Lew;
Receptor Cross-Talk;
Receptors, Cholinergic;
immunology;
T-Lymphocytes, Helper-Inducer;
immunology
- From:
Neuroscience Bulletin
2019;35(3):507-518
- CountryChina
- Language:English
-
Abstract:
Myasthenia gravis (MG) is a prototypical antibody-mediated neurological autoimmune disease with the involvement of humoral immune responses in its pathogenesis. T follicular helper (Tfh) cells have been implicated in many autoimmune diseases. However, whether and how Tfh cells are involved in MG remain unclear. Here, we established and studied a widely-used and approved animal model of human MG, the rat model with acetylcholine receptor alpha (AChRα) subunit (R-AChR)-induced experimental autoimmune myasthenia gravis (EAMG). This model presented mild body-weight loss 10 days after the first immunization (representing the early stage of disease) and more obvious clinical manifestations and body-weight loss 7 days after the second immunization (representing the late stage of disease). AChR-specific pre-Tfh cells and mature Tfh cells were detected in these two stages, respectively. In co-cultures of Tfh cells and B cells, the number of IgG2b-secreting B cells and the level of anti-AChR antibodies in the supernatant were higher in the cultures containing EAMG-derived Tfh cells. In immunohistochemistry and immunofluorescence assays, a substantial number of CD4/Bcl-6 T cells and a greater number of larger germinal centers were observed in lymph node tissues resected from EAMG rats. Based on these results, we hypothesize that an AChR-specific Tfh cell-mediated humoral immune response contributes to the development of EAMG.
