Natural Antibodies

Natural antibodies are those antibodies present in the circulation of vertebrates that have not been previously exposed to specific antigens [1]. Natural antibodies were identified at the beginning of 20th century in the sera of humans or laboratory animals that had not been specifically immunized [1]. The best characterized and studied natural antibodies are those directed against blood group substances; it was reported that individuals with “0” blood group/type had sera/plasma antibodies against A and B antigens, whereas individuals of A group only have anti- B antibodies and vice versa [2, 3]. This puzzling observation was difficult to explain because it was not known that blood group substances contain epitopes shared with microorganisms living in the gut of the individuals. Another observation was related to the relative “tolerance” of the individuals to their own blood group antigens because, at that time, no auto-antibodies were detected under normal circumstances. Using more sensitive methods it has been established that natural antibodies are present in the sera/plasma of normal healthy individuals and that these antibodies may have a physiological role connecting the immune system and may participate in the removal of aging cells, miss folded proteins, etc. [3–8]. Some characteristics of natural antibodies have been described over the years. Most natural antibodies are the IgM isotype, although other isotypes, such as IgG and IgA, are also present. Natural antibodies are germ line encoded, meaning that under normal circumstances they do not contain mutations in their variable regions. Natural antibodies have polyreactive binding sites, which imply that these antibodies may bind different epitopes with different structure/conformation. Due to their polyreactivity, natural antibodies often bind with low to medium affinity (10⁵–10⁷ M⁻¹) [4, 5, 9, 10]. As mentioned above, the specificity of these antibodies is directed against normal microbiota, but some clearly recognize self-antigens. Natural antibodies may also have a role in protection against invading microorganisms [7, 8, 11–15].