Properties and biological functions of natural antibodies

A series of studies has provided a better definition of several of the properties of natural antibodies. Polyreactive but also monoreactive natural antibodies are encoded by nonmutated or minimally mutated germ-line genes. Usually, but not always, natural antibodies possess low affinities but high avidities, and each one of them corresponds to the product of a single clone. Expression of natural antibody reactivity seems to be under the control of T cells.

Polyreactive natural antibodies carry common idiotypes and establish a dense idiotypic network among themselves early in ontogeny.

Natural antibodies have been reported to effect various biological functions (Table 1). Depending on the situation, they can play either a physiological, i.e. beneficial, or a pathological, i.e. harmful, role. Treatment of mice with idiotypically interconnected monoclonal antibodies or anti-idiotype antibodies to natural antibodies results in an increase or decrease

Table 1 Biological functions of natural antibodies

Immunoregulation through idiotypic interactions Immunoregulation by interacting with cytokines Immunoregulation by interacting with B and T cells Antigen processing and presentation by B lymphocytes Rejection or protection of cellular engraftments Interference with the development of autoimmune states Induction of autoimmune-like syndromes Induction of glomerulonephritis Tumor inhibition or enhancement Clearance of altered self constituents Elimination or protection of pathogens Expression of catalytic or inhibitory activities of the immune response according to the idiotypes involved. In normal humans and mice, a natural antibody idiotypic-like network exists that regulates the binding of IgG autoantibodies to self antigens, and this network is deficient in autoimmune states. Moreover, natural antibodies able to interact with molecules present on the surface of B and T cells have been shown to inhibit B cell growth or to suppress activation of T cell or autologous mixed lymphocyte reactions. Similarly, natural antibodies to various cytokines possess immunoregulatory functions.

B cells that bear natural antibodies as receptors have been shown to play an important role in the processing and presentation of antigens. Natural antibodies able to enhance tissue rejection but also, in contrast, to increase graft survival have been detected. By binding to altered self constituents, natural antibodies contribute to the clearance of catabolic products from the organism. Similarly, by reacting with pathogenic agents, they increase the opsonization of the latter by the reticuloendothelium system and contribute in their elimination from the organism. In some instances, natural antibodies can also inhibit the pathogenic effect by interacting with the host components rather than with the pathogen itself.

On the other hand, by binding to pathogens, natural antibodies focus the complement attack on non-lethal sites and protect the pathogen from destruction. Furthermore, they can even promote pathogenesis by mediating the internalization of the pathogens to gain access to its cellular niche. Likewise, depending on the situation, natural antibodies reacting with malignant cells enhance, retard or have no effect on tumor development.

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