A schematic model representing a continuous autoimmune loop carried out by macrophage, β₂GPI-reactive CD4⁺ T cell, and anti-β₂GPI antibody–producing B cell. The macrophage efficiently presents the cryptic β₂GPI determinant in the context of HLA-DR. The β₂GPI-reactive CD4⁺ T cell is activated by recognition of the cryptic β₂GPI peptide and exerts helper activity that induces production of IgG anti-β₂GPI autoantibodies from the specific B cell. The immune complex consisting of anionic surfaces, β₂GPI, and IgG anti-β₂GPI antibodies were captured by macrophages via FcγRI.