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[Autoantibodies, tolerance and autoimmunity]
Pablo Oppezzo1, Guillaume Dighiero
1Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur, 28, rue du Dr Roux, 75724 Paris, France.
Pathologie-Biologie
|October 22, 2003
Summary
Natural autoantibodies (NAA) are produced by autoreactive B cells, challenging the clonal deletion theory of self-tolerance. While clonal deletion explains some self-tolerance, the production of NAA against certain self-antigens remains unexplained.
Area of Science:
- Immunology
- Autoimmunity research
- B cell biology
Context:
- Historical concepts of autoimmunity include Metchnikoff's autoimmunization and Ehrlich's horror autotoxicus.
- The clonal deletion theory, supported by Landsteiner, Burnett, and Medawar, has been the primary explanation for self-tolerance.
- Recent findings reveal a substantial repertoire of autoreactive B cells producing natural autoantibodies (NAA).
Purpose:
- To re-evaluate the clonal deletion theory in light of new findings on natural autoantibodies.
- To explore the characteristics and implications of the autoreactive B-cell repertoire.
- To investigate the mechanisms underlying self-tolerance and autoimmunity.
Summary:
- Autoreactive B cells are a significant part of the B-cell repertoire and produce natural autoantibodies (NAA) with broad reactivity against conserved epitopes.
- NAA are self-reactive but not self-specific, challenging the notion that all self-reactive cells are eliminated via clonal deletion.
- While clonal deletion likely explains the absence of antibodies against critical determinants like ABO blood groups, the production of anti-I antibodies in healthy individuals remains an open question.
Impact:
- The existence of NAA necessitates a revision of current models of self-tolerance.
- Understanding NAA production may offer new insights into autoimmune diseases.
- Further research is needed to elucidate the mechanisms governing the deletion of B cells against specific self-antigens.