The effect of Toll-like receptor 4 on β2-glycoprotein I-induced B cell activation in mouse model. (March 2016)

• Record Type: Journal Article
• Authors: Cheng, Si; He, Chao; Zhou, Hong; Kong, Xiangmin; Xie, Hongxiang; Xia, Longfei; Yan, Jinchuan
• Is Part Of: Molecular immunology. Volume 71(2016:Mar.)
• Page Start: 78
• Page End: 86
• Publication Date: 2016-03
• Subjects: APS antiphospholipid syndrome -- aPL antiphospholipid antibodies -- β2GPI β2-glycoprotein I -- TLR4 loll-like receptor 4 -- BMDCs marrow-derived dendritic cells -- APCs antigen-presenting cells -- IL-6 interleukin 6 -- IL-10 interleukin 10 -- PAMPs pathogen-associated molecular patterns -- DAMPs damage-associated molecular patterns -- MHC II MHC class II molecules; Antiphospholipid syndrome -- β2-glycoprotein I -- Antiphospholipid antibodies -- TLR4 -- B lymphocytes; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2016.01.012
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: TLR4 is required for the activation of B cells and the production of anti-β2 GPI antibody in mice treated with β2 GPI. TLR4-related events are involved in β2 GPI-mediated pathogenic effects in antiphospholipid syndrome (APS). Compared with other antigens, β2 GPI is more closely involved in APS, which cause the activation of B cells. 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 (β2 GPI). However, the roles of TLR4 in the activation of B cells and production of anti-β2 GPI 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 β2 GPI. After β2 GPI injection, the level of anti-β2 GPI 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-β2 GPI antibody titer and more germinal centers in C3H/HeN mice. Moreover, the β2 GPI-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 β2 GPI-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 β2 GPI, but the immunological mechanisms of antiphospholipid syndrome (APS) need further investigation.