The Role of TLR4 on B Cell Activation and Anti-GPI Antibody Production in the Antiphospholipid Syndrome

Figure 1

The model for antigen-triggered B cell activation. A model was proposed for B cell-mediated, TLR4-dependent roles of phospholipid-binding protein (human β₂GPI), and innate immune activation in the development of APS-related autoantibodies. This figure outlines two approaches in the process leading to the development of anti-β₂GPI autoantibodies: (a) TD-Ag pathway: Stage 1, activation of DCs and human β₂GPI-specific T cells, Stage 2, activation of human β₂GPI-specific B cells, and Stage 3, the production of anti-β₂GPI autoantibodies and cytokine. (b) TI-Ag pathway: B cell tolerance is broken down in human β₂GPI-specific B cells that recognize self-Ags (human β₂GPI). Then, these B cells present human β₂GPI to any human β₂GPI-specific T cells that can recognize a self-Ag epitope recognized by the B cells, leading to the activation of human β₂GPI-specific T cells. These activated T cells provide help to the cognate B cells, leading to the production of anti-β₂GPI autoantibodies. At last, the activated B cells can present various self-Ag epitopes to T cells with different specificity allowing them in turn to promote the activation of additional human β₂GPI-specific B cells.