Polyreactive Antibodies Bind to HIV-Induced Apoptotic Cells and Enhance Complement-Mediated Phagocytosis by Macrophages

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NIDCR	IMMUNO-17

Authors

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

Abstract

Polyreactive antibodies are a major component of the natural antibody repertoire and bind a variety of structurally unrelated antigens. Many of the properties attributed to natural antibodies are, in fact, due to polyreactive antibodies. In this context, millions of cells in the body undergo apoptosis daily and natural antibodies bind to these cells. In the present experiments, we show that it is the polyreactive and not the monoreactive antibodies in the natural antibody repertoire that bind to apoptotic cells. We further show that although polyreactive antibodies bind only minimally (3.0 to 18%) to early apoptotic cells, they bind to the membrane and cytoplasm of nearly 90% of late apoptotic cells. FACS analysis and ImageStream revealed that apoptotic cells treated with polyreactive antibodies also bind complement, generate the anaphylatoxin C5a and are phagocytosed by macrophages at a two-to-five fold higher frequency than cells treated with monoreactive antibodies. Of particular interest, cells made apoptotic by HIV also bind polyreactive antibodies and are phagocytosed by macrophages. We conclude that polyreactive antibodies are an important component of the natural/innate immune system and regulate the clearance of cells made apoptotic through either natural endogenous processes or as a result of infection.

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