Occurrence and general characteristics of natural antibodies

A series of studies have shown that natural antibodies of the immunoglobulin M (IgM), IgG and IgA isotopes directed against an immense variety of antigens are present in normal sera of humans and other animal species including various fish of very distant phylogenetic orders (e.g. shark, torpedo, sturgeon and salmon). Internal, cell surface and circulating proteins, carbohydrates, nucleic acids, lipids and haptens are recognized by these natural antibodies. These constituents represent ubiquitous, self or highly conserved antigens and also environmental foreign antigens. IgM and IgG natural antibodies reacting with cell surface molecules of the immunoglobulin superfamily have been repeatedly detected in normal sera. Often IgG natural antibody activity was partially or completely masked in whole serum but it was unambiguously revealed after appropriate treatment of the serum. Depending on the antigen used, 5-100% of the normal sera examined were found to contain antibodies directed against a given antigen.

Human and mouse sera analyzed by means of ELISA or immunoblotting using homologous tissue extracts as the antigen source exhibited distinct IgM and IgG autoreactivity profiles. Two types of antibodies were found and isolated from normal sera: those that react with more than two, apparently unrelated antigens and those specific to a single antigen. Polyreactive antibodies are by far the most abundantly found in normal sera and usually possess low affinities. Monospecific antibodies behaved like the experimentally induced antibodies and usually possessed high affinities.

Similarly, B cell clones prepared from various human and mouse lymphoid organs during fetal and adult life secreted monoclonal natural antibodies reacting with a wide variety of self and nonself antigens. Depending on the stage of development and the lymphoid organ, 2-100% of all the clones secreting immunoglobulins synthesized natural autoantibodies and, among them 2.5-100% reacted with two or more self and nonself antigens. The natural antibodies are produced by conventional B lymphocytes, although in some instances, it has been reported that Ly-1+ B cells were preferentially involved in their synthesis. Natural IgM autoantibody-producing B cell clones have also been obtained from nude, germ-free and antigen-free mice. Recently antibodies able to recognize self antigens with high specificity were isolated from a phage display library composed of the rearranged V genes of peripheral blood lymphocytes from a normal individual.

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