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Peripheral Tolerance and Organ Specific Autoimmunity

  • Harald von Boehmer
  • Elmar Jaeckel
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 490)

Abstract

Concepts of specific immunotolerance were first introduced after the clonal selection theory gained acceptance. In early days Burnet and Lederberg formulated the simple concept that there was a fundamental difference between immature and mature, antigen-receptor bearing lymphocytes such that binding of antigen by the former would result in cell death, while binding to the latter would result in gain of effector function. At that time it was not known that immunocytes developed in distinct anatomical sites and thus would perhaps not encounter all self antigens as if they were circulating in the organism like mature lymphocytes. Even then this concept would fail to deal with proteins expressed only in adulthood. Nevertheless, this was the first theory of recessive tolerance that gained experimental support and by now is an established fact. A variant of that theme is the recently discovered receptor-deletion whereby immature B but not T cells change their receptors when confronted with antigen, perhaps because the antigen keeps the rearrangement process ongoing whereby already productive genes are deleted and new ones are being generated. Thus we have clonal or cellular deletion as well as receptor editing of immature lymphocytes as possible mechanism that affect immature lymphocytes whereby unresponsiveness is achieved without prior activation to effector function i.e. cytokine secretion, cytolytic activity or antibody production.

Keywords

Molecular Mimicry Oral Tolerance Nonobese Diabetic Mouse Activation Induce Cell Death Receptor Editing 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Harald von Boehmer
    • 1
  • Elmar Jaeckel
    • 1
  1. 1.Department of Cancer Immunology & AIDSHarvard Medical School Dana-Farber Cancer InstituteBostonUSA

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