title: The effect of Toll-like receptor 4 on β2-glycoprotein I-induced B cell activation in mouse model.
abstract: Our previous study demonstrated that Toll-like receptor 4 (TLR4) plays a vital role in the maturation of bone marrow-derived dendritic cells (BMDCs) from the mice immunized with human β2-glycoprotein I (β2GPI). However, the roles of TLR4 in the activation of B cells and production of anti-β2GPI antibodies in vivo have been rarely studied. This study aimed to investigate the activation of B cells from TLR4-defective (C3H/HeJ) and TLR4-intact (C3H/HeN) mice pre-immunized with human β2GPI. After β2GPI injection, the level of anti-β2GPI antibody in the serum of TLR4-defective and TLR4-intact mice was gradually increased and the number and size of germinal centers in the spleen were also significantly increased. Compared with C3H/HeJ mice, we observed significantly higher anti-β2GPI antibody titer and more germinal centers in C3H/HeN mice. Moreover, the β2GPI-induced expression of CD40L, CD40, CD80, CD86 and MHC II in C3H/HeN mice was significantly higher than that in C3H/HeJ mice. Furthermore, the β2GPI-induced expression of B cell activating factor (BAFF) in the spleen and IL-6 and IL-10 in B cells from C3H/HeN mice was also significantly increased compared to C3H/HeJ mice. Taken together, our results suggest that TLR4 is required for the activation of B cells and the production of autoantibody in mice treated with β2GPI, but the immunological mechanisms of antiphospholipid syndrome (APS) need further investigation.
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Si
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. Electronic address: hongzhou@ujs.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China. Electronic address: yanjinchuan@hotmail.com.
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Yan
mesh_terms: D000818:Animals; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D053482:beta 2-Glycoprotein I / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D053482:beta 2-Glycoprotein I
keywords: Antiphospholipid antibodies; Antiphospholipid syndrome; B lymphocytes; TLR4; β(2)-glycoprotein I