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.

Interrogation of individual intratumoral B lymphocytes from lung cancer patients for molecular target discovery

“…In newborns, 50 % of cord B cells express polyreactive antibodies [48], and in adults, 15-20 % of peripheral B cells express polyreactive antibodies [34]. Interestingly, polyreactive antibodies in the circulation appear to have broad antimicrobial properties [49]. It is intriguing to speculate that polyreactive antibodies in tumors may, in the aggregate, have antitumor properties.…”

Impact of Natural IgM Concentration on Gene Therapy with Adenovirus Type 5 Vectors

“…One example of a polyreactive IgM is monoclonal antibody 2E4, which recognizes multiple distinct antigens (21). Interestingly, we found that both 2E4 and BALB/c natural IgM could bind both to Ad5 and to an unrelated antigen: dinitrophenol coupled to bovine serum albumin (DNP-BSA) (Fig.…”

A Cryptic Polyreactive Antibody Recognizes Distinct Clades of HIV-1 Glycoprotein 120 by an Identical Binding Mechanism

“…The polyreactivity of Abs and B cell receptors is believed to contribute to the diversification of the immune repertoire and endows the immune system with the ability to bind, and respond, to virtually any potential antigen at a given time (2)(3)(4). Circulating polyreactive Abs found under physiological conditions, especially those also present in preimmune repertoires, have been proposed to constitute a first line of defense against pathogens and to participate in the maintenance of immune homeostasis (1,(5)(6)(7)(8). Various pathological conditions, including different autoimmune diseases and viral infections, have been associated with an expansion of the repertoires of polyreactive Abs (9 -12).…”