title: Polyreactive antibodies plus complement enhance the phagocytosis of cells made apoptotic by UV-light or HIV.
abstract: Polyreactive antibodies are a major component of the natural antibody repertoire and are capable of binding a variety of structurally unrelated antigens. Many of the properties attributed to natural antibodies, in fact, are turning out to be due to polyreactive antibodies. In humans, each day, billions of cells undergo apoptosis. In the present experiments, we show by ImageStream technology that although polyreactive antibodies do not bind to live T cells they bind to both the plasma membrane and cytoplasm of late apoptotic cells, fix complement, generate the anaphylatoxin C5a and increase by as much as 5 fold complement-mediated phagocytosis by macrophages. Of particular importance, T cells undergoing apoptosis following infection with HIV also bind polyreactive antibodies and are phagocytosed. We conclude that the polyreactive antibodies in the natural antibody repertoire contribute in a major way to the clearance of cells made apoptotic by a variety of natural and infectious processes.
authors.affiliation: Division of Monoclonal Antibodies, OBP, OPS, CDER, FDA.
authors.forename: Zhao-hua
authors.initials: ZH
authors.lastname: Zhou
authors.forename: Teresa
authors.initials: T
authors.lastname: Wild
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
authors.forename: Laine H
authors.initials: LH
authors.lastname: Sylvers
authors.forename: Yahong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Luxia
authors.initials: L
authors.lastname: Zhang
authors.forename: Larry
authors.initials: L
authors.lastname: Wahl
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Wahl
authors.forename: Steven
authors.initials: S
authors.lastname: Kozlowski
authors.forename: Abner L
authors.initials: AL
authors.lastname: Notkins
mesh_terms: D000706:Anaphylatoxins / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology* / Q000528:radiation effects*; D015936:Complement C5a / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D006678:HIV / Q000502:physiology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D010587:Phagocytosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D000706:Anaphylatoxins; D000906:Antibodies; D007075:Immunoglobulin M; D015936:Complement C5a; D003165:Complement System Proteins