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Central tolerance


Central tolerance is the mechanism by which newly developing T cells and B cells are rendered non-reactive to self.[1] The process is required due to the random generation of receptor specificities that occurs during T cell and B cell differentiation, whereby a proportion of the cells generated are self-reactive (recognise the component self antigens of the host).

In mammals the process occurs in the thymus (T cells)[2][3] and bone marrow (B cells), when maturing lymphocytes are exposed to self antigens. Self antigens are present in both organs due to endogenous expression within the organ and importation of antigen due to circulation from peripheral sites. In the case of T cell central tolerance, additional sources of antigen are made available in the thymus by the action of the transcription factor AIRE.

After exposure to self antigens, T cells and B cells become immunologically tolerant (non-reactive) in a number of ways :

Genetic defects in these processes lead to autoimmunity, such as in the human syndromes APS-1 and IPEX.

References

  1. ^ http://www-immuno.path.cam.ac.uk/~immuno/part1/lec11/lec11_97.html
  2. ^ Sprent J, Kishimoto H (2001). "The thymus and central tolerance". Philos Trans R Soc Lond B Biol Sci 356 (1409): 609-16. PMID 11375064.
  3. ^ Hogquist K, Baldwin T, Jameson S (2005). "Central tolerance: learning self-control in the thymus". Nat Rev Immunol 5 (10): 772-82. PMID 16200080.
  4. ^ Halverson R, Torres R, Pelanda R (2004). "Receptor editing is the main mechanism of B cell tolerance toward membrane antigens". Nat Immunol 5 (6): 645-50. PMID 15156139.

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