Standard Article

Natural Antibodies

  1. Moncef Zouali1,2

Published Online: 15 SEP 2009

DOI: 10.1002/9780470015902.a0001213.pub2



How to Cite

Zouali, M. 2009. Natural Antibodies. eLS. .

Author Information

  1. 1

    Institut National de la Recherche et de la Santé Médicale (Inserm), Paris, France

  2. 2

    University Ren Diderot Paris, Paris, France

Publication History

  1. Published Online: 15 SEP 2009

This is not the most recent version of the article. View current version (23 DEC 2015)


Natural antibodies are essentially antibodies of the immunoglobulin M (IgM) isotype present in the circulation of normal humans and other mammalian species that have not been previously exposed to deliberate immunization. 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 antigen to the immune system. Natural antibodies are frequently directed to intracellular structures, rather than to cell-surface antigens. They have been found to play a role in protection against infectious agents and to exert homeostatic functions. Other investigations suggest that natural antibodies might play a pathogenic role.

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, recognizing 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.


  • autoimmunity;
  • tolerance;
  • immunoglobulin genes;
  • B-1a cells;
  • marginal zone B cells;
  • autoimmune disease