Immunization with an apoptotic cell-binding protein recapitulates the nephritis and sequential autoantibody emergence of systemic lupus erythematosus

Jerrold S. Levine, Rebecca Subang, Samih H. Nasr, Sylvie Fournier, Ginette Lajoie, Joan Wither, Joyce Rauch

Research output: Contribution to journalArticle

35 Scopus citations


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 β2-glycoprotein I, an apoptotic cell-binding protein, in the presence of LPS induces a long-lived, potent response to β2- 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.

Original languageEnglish (US)
Pages (from-to)6504-6516
Number of pages13
JournalJournal of Immunology
Issue number9
StatePublished - Nov 1 2006


ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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