Central tolerance

In immunology, central tolerance (also known as negative selection) is the process of eliminating any developing T or B lymphocytes that are autoreactive, i.e. reactive to the body itself.

[2] Lymphocyte maturation (and central tolerance) occurs in primary lymphoid organs such as the bone marrow and the thymus.

[1] The production of random TCRs and BCRs is an important method of defense against microbes due to their high mutation rate.

For example, lack of functional RAG1/2, enzymes necessary for somatic recombination, has been linked to development of immune cytopenias in which antibodies are produced against the patient's blood cells.

[4] Due to the nature of a random receptor recombination, there will be some BCRs and TCRs produced that recognize self antigens as foreign.

[2] This is problematic, since these B and T cells would, if activated, mount an immune response against self if not killed or inactivated by central tolerance mechanisms.

[5][page needed] Therefore, without central tolerance, the immune system could attack self, which is not sustainable and could result in an autoimmune disorder.

[3][page needed] The result of central tolerance is a population of lymphocytes that do not mount immune response towards self-antigens.

[6][7] The mechanism has its name because it selects for survival only those thymocytes whose TCRs do interact with peptide-MHC complexes on antigen presenting cells in the thymus.

During the late stage of positive selection, another process called "MHC restricition" (or lineage commitment) takes place.