Natural antibodies – facts known and unknown

Abstract

In contrast to adaptive antibodies, natural antibodies are present in a non-immunised organism from birth, and they do not include anti-Gal antibodies and/or anti-Gal natural antibodies, which are developed as a result of the effect of the α-Gal epitope and physiological flora. Natural antibodies are the first line of the organism’s defence before the formation of the immunity created via the stimulation of elements that determine specific and non-specific immunity. This is especially important in the case of infants. Despite the fact that natural antibodies differ in their function from adaptive antibodies, they are polyreactive and they detect autoantigens and new antigenic determinants. Natural antibodies are formed from the subpopulation of B lymphocytes, mainly B1 lymphocytes and B lymphocytes of the marginal zone. This phenomenon is supported by the fact that when the quantity of these cells in the organism decreases, which happens with age, the level of natural antibodies also decreases and the risk of illnesses of old age becomes higher. During ontogenesis, these antibodies participate in many physiological processes, including the “support” of the immune system and homeostasis, the prevention of inflammation, infections and other pathological states, such as autoimmune and cardiovascular diseases, or the process of carcinogenesis. The best known natural antibody is IgM, but the role of IgGs and IgAs is also considered important. Nowadays, many researchers also mention intravenous immunoglobulins, which are used in the treatment of numerous illnesses, and there are discussions on the possibility of increasing their potential if they were based on natural antibodies.

Antibody response against HERV-W in patients with MOG-IgG associated disorders, multiple sclerosis and NMOSD

“…Why this particular response occurs is unclear. Based on existing studies (Avrameas and Selmi, 2014;Palma et al, 2018), it may involve different levels of natural autoantibodies that may directly be linked to a different embryonic (perinatal) thymus exposure to the endogenous HERV-W envelope, which would be decreased or defective in such individuals. Moreover, it should be relevant to note that the antibody response we documented in the study does not have the magnitude of antibody response to infectious agents, when the adaptive immune system is involved in an antibody response to exogenous antigens.…”

Mechanisms of sex hormones in autoimmunity: focus on EAE

“…When such a response is directed against self-tissues, autoimmunity may ensue. However, healthy individuals can have signatures of autoimmune response as evidenced by the detection of low levels of antibodies and T cells against autoantigens that may reflect formation of natural antibodies or idiotypic networks [1][2][3][4]. Autoimmune diseases (AIDs) are clinically manifested when autoimmunity leads to tissue damage disrupting the functions of affected organs [5,6].…”

Natural Autoantibodies in Chronic Pulmonary Diseases

“…However, recent studies have shown that sera of patients with or without autoimmune diseases contain IgG autoAbs that react with a set of self-antigens and are unique to each disease [7,8]. These so-called natural autoAbs usually react with intracellular proteins and long non-coding RNAs, and are thought to have evolved as an adaptive mechanism for functions such as debris clearance, which is consistent with their utility as diagnostic and prognostic indicators of disease [8].…”

“…For about 50 years since the discovery of natural IgG autoAbs, it was generally thought that they had a low affinity for autoantigens; therefore, the role of natural IgG autoAbs has remained unclear [7]. However, recent studies have revealed that natural IgG autoAbs are not non-reactive, rather they have a fundamental role in systemic innate immune responses [8].…”