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 beta2-glycoprotein 1 (beta(2)GPI) 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(2)GPI 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 F(1) mice self-sustaining autoimmunity against the beta(2)GPI, either associated to apoptotic cells or macropinocytosed from the serum.
Bondanza
Attilio
A
H San Raffaele Scientific Institute, Università Vita-Salute, Milano, Italy.
Rovere-Querini
Patrizia
P
Zimmermann
Valérie S
VS
Balestrieri
Genesio
G
Tincani
Angela
A
Sabbadini
Maria Grazia
MG
Manfredi
Angelo A
AA
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D002417:Cattle; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005260:Female; D007114:Immunization; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D010873:Pinocytosis / Q000276:immunology*; D014183:Transplantation, Heterologous; D014185:Transplantation, Isogeneic; D053482:beta 2-Glycoprotein I / Q000276:immunology*
D017152:Antibodies, Antiphospholipid; D053482:beta 2-Glycoprotein I