A mechanism for the generation of self-tolerance

David Allison, Thomas McKearn

Research output: Contribution to journalArticle

Abstract

We propose that immunologic tolerance to self-antigens is due to the production of specific antibody against the antigen combining sites in the receptors of self-reactive lymphoid cells. Generation of this suppressive antibody is dependent upon an early auto-aggressive response in which proliferation of self-reactive lymphoid clones quantitatively favors presentation of their receptors as antigens. Combining sites are qualitatively good antigens in the pretolerant animal because they are associated with antigens that can serve as recognition sites for those thymic lymphocytes that are necessary to trigger the production of antibody. Thus, self-antigens adjacent to combining sites can serve as carriers to promote antibody responses against the combining sites. Antibody generated against the self-reactive combining sites in this early interval suppresses the self-reactive cells and establishes tolerance. We postulate that, after tolerance has been established, the immune response is regulated primarily by the interactions between receptors, foreign antigen, and antigen-specific antibody. This theory on the generation of tolerance by production of antibody to combining sites would explain a number of observations on graft-versus-host disease, neonatal chimeric tolerance, establishment of new transplantation tolerance in adult radiation chimeras, and the failure of young animals to produce significant amounts of antibody against foreign antigens.

Original languageEnglish (US)
Pages (from-to)201-206
Number of pages6
JournalJournal of Theoretical Biology
Volume54
Issue number2
DOIs
StatePublished - 1975
Externally publishedYes

Fingerprint

Self Tolerance
Antigens
Antibody
Tolerance
Antibodies
Binding Sites
antigens
Antibody Formation
Antigen Receptors
antibodies
Autoantigens
Receptor
Radiation Chimera
antibody formation
Lymphocytes
Transplantation Tolerance
Animals
receptors
Graft vs Host Disease
Transplantation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Applied Mathematics
  • Modeling and Simulation
  • Statistics and Probability
  • Medicine(all)

Cite this

A mechanism for the generation of self-tolerance. / Allison, David; McKearn, Thomas.

In: Journal of Theoretical Biology, Vol. 54, No. 2, 1975, p. 201-206.

Research output: Contribution to journalArticle

Allison, David ; McKearn, Thomas. / A mechanism for the generation of self-tolerance. In: Journal of Theoretical Biology. 1975 ; Vol. 54, No. 2. pp. 201-206.
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