The broad antibacterial activity of the natural antibody repertoire is due to polyreactive antibodies.
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.
Zhou
Zhao-Hua
ZH
Experimental Medicine Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
Zhang
Yahong
Y
Hu
Ya-Fang
YF
Wahl
Larry M
LM
Cisar
John O
JO
Notkins
Abner Louis
AL
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
D000706:Anaphylatoxins; D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D003165:Complement System Proteins