Glimpses into the Balance Between Immunity and Self-Tolerance

  1. Gregory R. Bock Organizer and
  2. Jamie A. Goode
  1. Christopher C. Goodnow

Published Online: 28 SEP 2007

DOI: 10.1002/9780470515280.ch13

Ciba Foundation Symposium 204 - The Molecular Basis of Cellular Defence Mechanisms

Ciba Foundation Symposium 204 - The Molecular Basis of Cellular Defence Mechanisms

How to Cite

Goodnow, C. C. (2007) Glimpses into the Balance Between Immunity and Self-Tolerance, in Ciba Foundation Symposium 204 - The Molecular Basis of Cellular Defence Mechanisms (eds G. R. Bock and J. A. Goode), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470515280.ch13

Author Information

  1. Howard Hughes Medical Institute and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305–5428, USA

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471965671

Online ISBN: 9780470515280

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Keywords:

  • immunity;
  • self-tolerance;
  • CD45 mutations;
  • lymphocyte clones;
  • clonal deletion thresholds

Summary

The need to maintain self-tolerance is at odds with the need to draw upon antibody and T cell receptor diversity to fight infection. Advances in genetic manipulation of the mouse have at last brought into view the clonal selection mechanisms that underpin self-tolerance, confirming in general terms the notion of clonal deletion and clonal anergy put forward by Burnet and Nossal. The image that has emerged, however, is much more sophisticated than could have been imagined, revealing that self-reactive clones are deleted or held back in a remarkable series of culling checkpoints placed at many steps along the pathway to antibody production. These checkpoints act in concert to balance the nature and size of the holes in the repertoire generated by self-tolerance against the need to draw upon as many clones as possible for immunity to infection. Spontaneous and induced mutations in the mouse, such as Fas, PTP1C and CD45 mutations, have just begun to yield a few glimpses into the molecular circuitry underpinning these cellular checkpoints. Much more extensive genetic analysis, made possible by the genome project, will be needed to illuminate the details of those circuits and the factors that lead them to fail in autoimmune disease.