Dendritic cells preferentially internalize apoptotic cells opsonized by anti-β2-glycoprotein I antibodies

Patrizia Rovere, Angelo A. Manfredi, Cristina Vallinoto, Valerie S. Zimmermann, Umberto Fascio, Genesio Balestrieri, Paola Ricciardi-Castagnoli, Claudio Rugarli, Angela Tincani, Maria Grazia Sabbadini

Research output: Contribution to journalArticlepeer-review

Abstract

Dendritic cells (DC) are potent antigen-presenting cells involved in the initiation of immune responses, including those directed towards self antigens, Immature DC capture soluble antigens by macropinocytosis or c-type lectin receptor-mediated endocytosis and particulate by phagocytosis, including Fc receptor-mediated phagocytosis. Apoptosis is accompanied by the clustering of intracellular autoantigens, which are also selectively cleaved and phosphorylated, and by the exposure of anionic phospholipids (phosphatidylserine, PS). Anti-phospholipid antibody (aPL) detection correlates with an increased risk of developing autoimmune syndromes. In this study apoptosis was induced by UV irradiation, growth factor deprivation or exposure to protein synthesis inhibitors of murine cells and verified by confocal microscopy and flow cytometry. Apoptotic cells were recognized by a panel of anti-β2-glycoprotein I (β2-GPI) aPL monoclonal antibodies, but not by isotype-matched antibodies. The binding restricted to membrane domains, corresponding to apoptotic blebs, was not affected by the stimulus initiating apoptosis and was specific, since it required the association of the β2-GPI co-factor to the apoptotic membrane. aPL-binding successfully transformed apoptotic cells in an efficient phagocytic substrate for murine immature DC, possibly skewing their immunogenicity in vivo.

Original languageEnglish
Pages (from-to)403-411
Number of pages9
JournalJournal of Autoimmunity
Volume11
Issue number5
DOIs
Publication statusPublished - Oct 1998

Keywords

  • Anti-phospholipid antibody
  • Anti-phospholipid antibody syndrome
  • Apoptosis
  • Dendritic cells
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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