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Clin Rev Allergy Immunol. 2019 Jun 3. doi: 10.1007/s12016-019-08746-9. [Epub ahead of print]

Natural Antibodies: from First-Line Defense Against Pathogens to Perpetual Immune Homeostasis.

Author information

1
Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Descartes, Sorbonne Paris Cité, 15 rue de l'Ecole de Médicine, F-75006, Paris, France.
2
United Nations Special Envoy for AIDS in Eastern Europe and Central Asia, Geneva, Switzerland.
3
Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Descartes, Sorbonne Paris Cité, 15 rue de l'Ecole de Médicine, F-75006, Paris, France. Srini.Kaveri@crc.jussieu.fr.

Abstract

Natural antibodies (nAbs) are most commonly defined as immunoglobulins present in the absence of pathological conditions or deliberate immunizations. Occurrence of nAbs in germ- and antigen-free mice suggest that their production is driven, at least in part, by self-antigens. Accordingly, nAbs are constituted of natural autoantibodies (nAAbs), and can belong to the IgM, IgG, or IgA subclasses. These nAbs provide immediate protection against infection while the adaptive arm of the immune system mounts a specific and long-term response. Beyond immediate protection from infection, nAbs have been shown to play various functional roles in the immune system, which include clearance of apoptotic debris, suppression of autoimmune and inflammatory responses, regulation of B cell responses, selection of the B cell repertoires, and regulation of B cell development. These various functions of nAbs are afforded by their reactivity, which is broad, cross-reactive, and shown to recognize evolutionarily fixed epitopes shared between foreign and self-antigens. Furthermore, nAbs have unique characteristics that also contribute to their functional roles and set them apart from antigen-specific antibodies. In further support for the role of nAbs in the protection against infections and in the maintenance of immune homeostasis, the therapeutic preparation of polyclonal immunoglobulins, intravenous immunoglobulin (IVIG), rich in nAbs is commonly used in the replacement therapy of primary and secondary immunodeficiencies and in the immunotherapy of a large number of autoimmune and inflammatory diseases. Here, we review several topics on nAbs features and functions, and therapeutic applications in human diseases.

KEYWORDS:

Autoimmunity; IVIG; Immune homeostasis; Intravenous immunoglobulin; Natural IgG; Natural IgM; Therapy

PMID:
31161341
DOI:
10.1007/s12016-019-08746-9

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