Immunization with an Apoptotic Cell-Binding Protein Recapitulates the Nephritis and Sequential Autoantibody Emergence of Systemic Lupus Erythematosus1

• Published in: The Journal of immunology (1950) Vol. 177; no. 9; pp. 6504 - 6516
• Main Authors: Levine, Jerrold S., Subang, Rebecca, Nasr, Samih H., Fournier, Sylvie, Lajoie, Ginette, Wither, Joan, Rauch, Joyce
• Format: Journal Article
• Language: English
• Published: 01.11.2006
• ISSN: 0022-1767; 1550-6606

The initial events predisposing to loss of tolerance in patients with systemic lupus erythematosus (SLE) are largely unknown, as are the events that precipitate the transition from preclinical to overt disease. We hypothesized that induction of murine SLE would require tipping the balance between tolerance and immunity in two ways: 1) an immunogen that could take advantage of apoptotic cells as a scaffold for epitope spread, and 2) an immune activator that would generate a strong and persistent T cell response to the inciting immunogen. We show that immunization of C57BL/6 and BALB/c mice with human β 2 -glycoprotein I, an apoptotic cell-binding protein, in the presence of LPS induces a long-lived, potent response to β 2 -glycoprotein I that results in epitope spread to multiple SLE autoantigens. SLE-specific autoantibodies emerged in a sequential manner that recapitulated the order seen in human SLE. Moreover, immunized mice developed overt glomerulonephritis closely resembling human lupus nephritis.