Requirement for dendritic cells in the establishment of anti-phospholipid antibodies

Objective: The cross-presentation of cell-associated autoantigens contributes to systemic autoimmune diseases, including systemic lupus erythematosus (SLE). Little is known about the regulation of the immune response against soluble autoantigens targeted in these diseases.

Methods: We immunized the offspring of New Zealand Black and New Zealand White mice (NZB × NZW F₁) with syngeneic dendritic cells (DC) that had macropinocytosed β2-glycoprotein 1 (β₂GPI) during propagation in normal mouse serum or that had phagocytosed apoptotic thymocytes with syngeneic (murine) or xenogeneic (bovine) β₂GPI, which was associated to plasma membrane of the cells. Mice were in parallel immunized with apoptotic thymocytes that had associated the β₂GPI to their membranes in the absence of DC. The development of anti-β₂GPI antibodies and clinical features were monitored.

Results. Apoptotic cells alone, opsonized with β₂GPI, failed to induce anti-β₂GPI autoantibodies or clinical disease. In contrast, autoimmunity developed in the presence of DC. Furthermore, the syngeneic β₂GPI was a more effective antigen than the xenogeneic protein in re-boosted animals.

Conclusions. DC effectively initiate in NZB × NZW F₁ mice self-sustaining autoimmunity against the β₂GPI, either associated to apoptotic cells or macropinocytosed from the serum.