B cell receptor editing in tolerance and autoimmunity.
Receptor editing is the process of ongoing antibody gene rearrangement in a lymphocyte that already has a functional antigen receptor. The expression of a functional antigen receptor will normally terminate further rearrangement (allelic exclusion). However, lymphocytes with autoreactive receptors have a chance at escaping negative regulation by "editing" the specificities of their receptors with additional antibody gene rearrangements. As such, editing complicates the Clonal Selection Hypothesis because edited cells are not simply endowed for life with a single, invariant antigen receptor. Furthermore, if the initial immunoglobulin gene is not inactivated during the editing process, allelic exclusion is violated and the B cell can exhibit two specificities. Here, we describe the discovery of editing, the pathways of receptor editing at the heavy (H) and light (L) chain loci, and current evidence regarding how and where editing happens and what effects it has on the antibody repertoire.
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. luning@mail.med.upenn.edu
Eline T
ET
Luning Prak
Marc
M
Monestier
Robert A
RA
Eisenberg
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015322:Gene Rearrangement, B-Lymphocyte / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D011947:Receptors, Antigen, B-Cell
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