Natural Antibodies

Abstract

Natural antibodies are essentially antibodies of the immunoglobulin M (IgM) isotype present in the circulation of normal humans and other mammalian species. They are detectable in the serum of healthy individuals before deliberate immunisation. They are often directed against highly conserved epitopes and often bind to ligands of varying chemical composition with low affinity. This antibody subset contrasts with immune antibodies, which are produced in response to the introduction of antigens to the immune system. Natural antibodies are frequently directed to intracellular structures, rather than to cell‐surface antigens. They have been found to play an innate‐like role in protection against infectious agents and to exert homeostatic functions in a variety of experimental models. Other investigations suggest that natural antibodies can play a pathogenic role in autoinflammatory diseases. Key Concepts A natural antibody is an antibody present in the circulation of an animal or a subject that had not been previously exposed to the corresponding antigen. Certain B‐lymphocyte subsets, such as B‐1a cells, are committed to natural antibody production. The antibody repertoire expressed in B‐cell malignancies exhibits several features in common with those of the natural antibody repertoire of healthy subjects. It is possible that natural antibody production is driven by microorganisms indigenous to the organism, such as bacteria living in the intestine. Natural antibodies play a role in shaping the B‐cell repertoire and may represent the precursors of antibodies to pathogens. Natural antibodies could serve as innate recognition receptors, recognising various bacterial cell‐wall components or parasites. Studies of rodents rendered deficient in natural antibodies suggest that this antibody subset is endowed with a homeostatic potential and housekeeping functions, such as recognition and removal of senescent cells and other self‐antigens. Circumstantial evidence suggests that natural antibodies can be associated with protection against Alzheimer disease, atherosclerosis or cancer development. B lymphocytes secreting natural antibodies could represent a reservoir capable of mutating their immunoglobulin variable region genes to give rise to high‐affinity pathogenic autoantibodies.

Exposure to the Epstein–Barr Viral Antigen Latent Membrane Protein 1 Induces Myelin-Reactive Antibodies In Vivo

“…In this study, we present evidence that anti-LMP1 antibodies in MBP-immunized mice are rather anti-MBP antibodies that obtain ability to cross-react with LMP1 during maturation process. This observation is in line with data suggesting that natural IgM in non-immunized animals able to recognize some conservative pathogen antigens ( 30 – 32 ). In contrast, induction of anti-MBP antibodies in LMP1-immunized mice is evidently a rare process, which requires epitope spreading.…”

Correlation of natural autoantibodies and cardiovascular disease-related anti-bacterial antibodies in pericardial fluid of cardiac surgery patients

“…Recently numerous studies have supported the role of the natural immune system, including natural autoantibodies, in the above functions as key players in the first line of defence against infections and clearance of apoptotic cells. Natural autoantibodies are present in the circulation of humans and other mammalian species without previous exposure to antigens , and are produced by B1 cells without somatic hypermutation; most of them are of IgM isotype. Natural autoantibodies of immunoglobulin (Ig)G isotype have also been described , which typically bind multiple self‐ and non‐self‐antigens.…”