title: The broad antibacterial activity of the natural antibody repertoire is due to polyreactive antibodies.
abstract: Polyreactive antibodies bind to a variety of structurally unrelated antigens. The function of these antibodies, however, has remained an enigma, and because of their low binding affinity their biological relevance has been questioned. Using a panel of monoclonal polyreactive antibodies, we showed that these antibodies can bind to both Gram-negative and Gram-positive bacteria and acting through the classical complement pathway can inhibit bacterial growth by lysis, generate anaphylatoxin C5a, enhance phagocytosis, and neutralize the functional activity of endotoxin. Polyreactive antibody-enriched, but not polyreactive antibody-reduced, IgM prepared from normal human serum displays antibacterial activity similar to that of monoclonal polyreactive IgM. We conclude that polyreactive antibodies are a major contributor to the broad antibacterial activity of the natural antibody repertoire.
authors.affiliation: Experimental Medicine Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Zhao-Hua
authors.initials: ZH
authors.lastname: Zhou
authors.forename: Yahong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Hu
authors.forename: Larry M
authors.initials: LM
authors.lastname: Wahl
authors.forename: John O
authors.initials: JO
authors.lastname: Cisar
authors.forename: Abner Louis
authors.initials: AL
authors.lastname: Notkins
mesh_terms: D000706:Anaphylatoxins / Q000276:immunology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001419:Bacteria / Q000276:immunology*; D003171:Complement Pathway, Classical / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis; D011485:Protein Binding
chemical_list: D000706:Anaphylatoxins; D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D003165:Complement System Proteins