DENDRITIC CELLS PREFERENTIALLY INTERNALIZE APOPTOTIC CELLS OPSONIZED BY ANTI-BETA-2-GLYCOPROTEIN-I ANTIBODIES

Dendritic cells (DC) are potent antigen-presenting cells involved in t he initiation of immune responses, including those directed towards se lf antigens. Immature DC capture soluble antigens by macropinocytosis or c-type lectin receptor-mediated endocytosis and particulate by phag ocytosis, including Fc receptor-mediated phagocytosis. Apoptosis is ac companied by the clustering of intracellular autoantigens, which are a lso selectively cleaved and phosphorylated, and by the exposure of ani onic phospholipids (phosphatidylserine, PS). Anti-phospholipid antibod y (aPL) detection correlates with an increased risk of developing auto immune syndromes. In this study apoptosis was induced by UV irradiatio n, growth factor deprivation or exposure to protein synthesis inhibito rs of murine cells and verified by confocal microscopy and now cytomet ry. Apoptotic cells were recognized by a panel of anti-beta 2-glycopro tein I (beta 2-GPI) aPL monoclonal antibodies, but not by isotype-matc hed antibodies. The binding restricted to membrane domains, correspond ing to apoptotic blebs, was not affected by the stimulus initiating ap optosis and was specific, since it required the association of the bet a 2-GPI co-factor to the apoptotic membrane. aPL-binding successfully transformed apoptotic cells in an efficient phagocytic substrate for m urine immature DC, possibly skewing their immunogenicity in vivo. (C) 1998 Academic Press