Binding and expediting clearance of apoptotic cells by natural polyreactive antibodies

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NIDCR	IMMUNO/INFLAM-33

Authors

• Z Zhou
• Y Xiong
• T Wild
• P Sylvers
• Y Zhang
• L Zhang
• L Wahl
• S Wahl
• S Kozlowski
• A Notkins

Abstract

It has been widely shown that ligands or “eat me” signals, including lipids, sugars and proteins are exposed on the surface of apoptotic cells. Since natural polyreactive antibodies can bind to a variety of self and non-self antigens, it was hypothesized that polyreactive antibodies may have a role in the clearance of apoptotic cells.In this study, various methods including UV light and HIV infection were used to put different types of cells into apoptosis. By flow cytometry, we found that monoclonal monoreactive antibodies showed little or no binding to apoptotic cells, while monoclonal polyreactive antibodies showed substantial binding to apoptotic cells. ImageStream techniques then were used to localize the binding sites of polyreactive antibodies within the apoptotic cells. In further experiments, with the macrophage cell line Raw 264.7, phagocytosis of human apoptotic cells was studied after polyreactive or monoreacitve antibodies were added to cell culture with or without complement. Both flow cytometry and ImageStream analysis clearly showed that polyreactive antibodies significantly enhanced the phagocytosis of apoptotic cells in the presence of complements. We conclude that the natural polyreactive antibodies can bind to various ligands exposed on/in apoptotic cells and thus may provide “bridging” with macrophages to engulf apoptotic cells.

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