Natural antibodies (NAbs) circulate in normal individuals in the absence of exogenous antigenic stimulation. In the mouse NAbs derive mainly from B-1 cells, a distinct B-cell subset found in the peritoneal and pleural cavities as well as the spleen. In contrast with B-2 cells, B-1 cells are positively selected against self-antigens. The repertoire of B-1 cell derived natural antibodies is characterized by a preferential usage of germline-encoded VH and VL genes, which lack N-region additions and is evolutionarily selected due to their importance for organisms’ survival and homeostasis. The natural antibody population rapidly recognizes and protects against pathogens that have not been encountered previously. On the other hand NAbs cross-react with several self-antigens and besides their role as first line defense against pathogens, it has been demonstrated they perform important “housekeeping” functions in healthy organisms. NAbs participate in the clearance of oxidative damaged structures and apoptotic cells, preventing the induction of pro-inflammatory effects. They also play a role in preventing the expansion of specific auto-reactive clones behaving as regulatory elements in acute or chronic inflammation.
Furthermore NAbs have shown to bind to ‘neo-self’ carbohydrate antigens on glycolipids and glycoproteins on malignant but not normal cells, which suggest they may take part in tumor immunosurveillance. Natural antibodies are believed to be essential for the immunoregulatory effects of intravenous immunoglobulin preparations (IVIg) increasingly used in the treatment of autoimmune and inflammatory diseases. To keep the non-pathogenic balance between these dual pathogen/self-antigen cross-reactivities a strict regulation in NAbs secretion and function is necessary in order to avoid autoimmune diseases. Actually, some of the NAbs related auto-reactivities, such as anti-DNA and anti-MOG, have been associated with autoimmunity in addition to the expansion of B-1 cells. However, B-1 cells’ direct role in autoimmune pathogenesis has not been completely established yet.
Many aspects regarding NAbs have yet to be studied in more detail: the reactivity and function of NAbs in health and different diseases, the behavior of this repertoire with increasing age, the regulation of natural antibody production and auto-reactivity, the ways to specifically activate NAbs producing B-1 cells with desired specificities, the characteristics of human NAbs, among others. This Frontiers research topic aims to encourage researchers to share their original data, hypotheses, future perspectives and commentaries regarding these and other aspects of NAbs biology in health and disease.
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