Proteomics

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6

IgM Abs to Apoptosis-associated Determinants recruit C1q and enhance dendritic cell phagocytosis of apoptotic cells


ABSTRACT: Natural antibodies, which arise without known immune exposure, have been described that specifically recognize cells dying from apoptosis but their role in innate immunity remains poorly understood. Herein, we show that the immune response to neo-antigenic determinants on apoptotic thymocytes is dominated by antibodies to oxidation-associated antigens, phosphorylcholine (PC), a head group that becomes exposed during programmed-cell death, and malondialdehyde (MDA), a reactive aldehyde degradation product of polyunsaturated lipids produced following exposure to reactive-oxidation species. While natural antibodies to apoptotic cells in naïve adult mice were dominated by PC and MDA specificities, the amounts of these antibodies were substantially boosted by treatment of mice with apoptotic cells. Moreover, the relative amounts of PC and MDA antibodies was affected by VH gene inheritance. Antibody interactions with apoptotic-cells also mediated the recruitment of C1q, which alone can promote apoptotic-cell phagocytosis by immature dendritic cells. Significantly, IgM-antibodies to both PC and MDA were primary factors in determining the efficiency of serum-dependent apoptotic-cell phagocytosis. Hence, we demonstrate a mechanism by which certain natural antibodies that recognize neo-antigens on apoptotic cells, in naïve mice and those induced by immune exposure to apoptotic-cells, can enhance the functional capabilities of immature dendritic cells for phagocytic engulfment of apoptotic cells. Keywords: Natural antibodies, Inflammation, Complement, Apoptosis In the study presented here, a total of 11 custom-spotted protein slides were hybridized with a T15 IgM monoclonal antibody at three different concentrations, an isotype control IgM, 2 slides were hybridized with serum from naїve mice, 2 slides incubated with serum from mice immunized with apoptotic cells, 2 slides were incubated with serum from mice immunized with saline, and a negative control slide with no antibody hybridized

SUBMITTER: Gregg J Silverman   Yifang Chen  Ekta Patel  Yong-beom Park  Gregg Silverman 

PROVIDER: E-GEOD-14958 | ArrayExpress | 2009-02-23

SECONDARY ACCESSION(S): GSE14958PRJNA111829

REPOSITORIES: GEO, ArrayExpress

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IgM antibodies to apoptosis-associated determinants recruit C1q and enhance dendritic cell phagocytosis of apoptotic cells.

Chen Yifang Y   Park Yong-Beom YB   Patel Ekta E   Silverman Gregg J GJ  

Journal of immunology (Baltimore, Md. : 1950) 20090501 10


Natural Abs, which arise without known immune exposure, have been described that specifically recognize cells dying from apoptosis, but their role in innate immunity remains poorly understood. Herein, we show that the immune response to neoantigenic determinants on apoptotic thymocytes is dominated by Abs to oxidation-associated Ags, phosphorylcholine (PC), a head group that becomes exposed during programmed cell death, and malondialdehyde (MDA), a reactive aldehyde degradation product of polyun  ...[more]

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