Pathophysiology of catalytic antibodies

doi:10.1016/j.imlet.2005.10.007

Immunology Letters

Volume 103, Issue 1, 28 February 2006, Pages 3-7

https://doi.org/10.1016/j.imlet.2005.10.007 Get rights and content

Abstract

Immunoglobulins have initially been illustrated as proteins produced by the immune system for binding and neutralizing foreign molecules potentially harmful to the organism. The number of V_H, D_H, J_H, V_L and J_L genes that encode the variable regions of immunoglobulins and the junctional diversity that occurs at the time of somatic rearrangement determine the extent of the repertoire of antibodies that may be potentially produced by an organism. This potential repertoire includes antibodies the antigen binding site of which may recognize external as well as autologous antigens, or may structurally resemble the active site of enzymes and be endowed with enzymatic activity. Under physiological conditions, B cell clones that produce antibodies naturally endowed with catalytic activity are negatively regulated and subjected to apoptosis. Catalytic antibodies are expressed only following active immunization, or if the physiological regulatory mechanisms that control the expression of catalytic antibody-producing B cell clones are perturbed, e.g. in the context of pregnancy or in the course of autoimmune diseases.

Section snippets

“On demand” production of catalytic antibodies

The concept that some antibodies may by endowed with catalytic activity was first proposed by Pauling in the early 1940s [1]. According to Pauling, if the structure of the antigen binding site of antibodies were to be produced in a random manner, the antigen binding site of some of the antibodies may resemble the active site of enzymes and the latter antibodies may express enzymatic activity. It is not until the development the hybridoma technology, which allows to produce antigen-specific

Spontaneous occurrence of catalytic antibodies

Catalytic antibodies may be generated spontaneously by the immune system, without deliberate immunization. The majority of the studies performed in human being have demonstrated that the prevalence of catalytic antibodies increases under pathological conditions and, in particular, in the context of autoimmune and inflammatory disorders. The first catalytic antibodies described were isolated from patients with asthma and were able to cleave the vasoactive intestinal peptide (VIP) [12]. Since

Proteolytic activity of natural catalytic antibodies

Catalytic antibodies of the IgG, IgA and IgM isotypes are part of the normal repertoire of circulating natural antibodies in healthy individuals [20], [21]. Whereas catalytic antibodies found under pathological conditions are directed towards particular antigenic substrates, i.e. DNA, RNA, Tg, FVIII, VIP or prothrombin, catalytic antibodies found under physiological conditions display polyreactivity and a broad specificity for different peptides. Levels of antigen-specific and polyreactive

Conclusion

Two types of catalytic antibodies can be distinguished (Fig. 4). Firstly, “induced” catalytic antibodies only appear upon active immunization using molecular mimics: the immunization with haptens that are analogs of transition states of chemical reactions, or with structures complementary to the active site of enzymes (variable regions of Ab1) would allow to fish out from a pool of available antibodies reactivities prone to acquire a catalytic activity during the process of affinity maturation.

Acknowledgments

Supported by Institut National de la Santé et de la Recherche Médicale, by Indian Council for Medical Research, by Centre Nationale de la Recherche Scientifique, by Indo-French Center for Promotion of Advanced Research, by ZLB Bioplasma AG (Bern, Switzerland) and by an award from Bayer HealthCare LLC (RTP, NC, USA).

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View full text

Short reviewPathophysiology of catalytic antibodies

Abstract

Section snippets

“On demand” production of catalytic antibodies

Spontaneous occurrence of catalytic antibodies

Proteolytic activity of natural catalytic antibodies

Conclusion

Acknowledgments

Immunol Lett

Immunol Today

FEBS Lett

Nature of forces between large molecules of biological interest

Nature

Catalytic antibodies

Science

Selective chemical catalysis by an antibody

Science

Reactive immunization

Science

A bait and switch hapten strategy generates catalytic antibodies for phosphodiester hydrolysis

Proc Natl Acad Sci USA

Antibody-catalyzed retro-aldol reaction

J Am Chem Soc

Organic synthesis supported by antibody catalytis

Synlett

Critical analysis of antibody catalysis

Annu Rev Biochem

Monoclonal anti-idiotypic antibodies as functional internal images of enzyme active sites: production of a catalytic antibody with a cholinesterase activity

Proc Natl Acad Sci USA

Functional mimicry: elicitation of a monoclonal anti-idiotypic antibody hydrolizing beta-lactams

FASEB J

Idiotypic network mimicry and antibody catalysis: lessons for the elicitation of efficient anti-idiotypic protease antibodies

J Immunol Methods

Short review
Pathophysiology of catalytic antibodies