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 x NZW F-1) with syngeneic dendritic cells (DC) that had macropinocytosed beta 2-glycoprotein 1 (beta 2GPI) during propagation in normal mouse serum or that had phagocytosed apoptotic thymocytes with syngeneic (murine) or xenogeneic (bovine) beta(2)GPI, which was associated to plasma membrane of the cells. Mice were in parallel immunized with apoptotic thymocytes that had associated the beta(2)GPI to their membranes in the absence of DC. The development of anti-beta 2GPI antibodies and clinical features were monitored. Results. Apoptotic cells alone, opsonized with beta(2)GPI, failed to induce anti- beta(2)GPI autoantibodies or clinical disease. In contrast, autoimmunity developed in the presence of DC. Furthermore, the syngeneic beta(2)GPI was a more effective antigen than the xenogeneic protein in re-boosted animals. Conclusions. DC effectively initiate in NZB x NZW F1 mice self-sustaining autoimmunity against the beta(2)GPI, either associated to apoptotic cells or macropinocytosed from the serum.