Receptor editing in lymphocyte development and central tolerance

  title={Receptor editing in lymphocyte development and central tolerance},
  author={David Nemazee},
  journal={Nature Reviews Immunology},
  • D. Nemazee
  • Published 1 October 2006
  • Biology
  • Nature Reviews Immunology
The specificities of lymphocytes for antigen are generated by a quasi-random process of gene rearrangement that often results in non-functional or autoreactive antigen receptors. Regulation of lymphocyte specificities involves not only the elimination of cells that display 'unsuitable' receptors for antigen but also the active genetic correction of these receptors by secondary recombination of the DNA. As I discuss here, an important mechanism for the genetic correction of antigen receptors is… 

B cell receptor editing in tolerance and autoimmunity

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 are described.

Functional development of the T cell receptor for antigen.

V(D)J recombination: of mice and sharks.

  • E. Hsu
  • Biology
    Advances in experimental medicine and biology
  • 2009
Studies in rabbit, chicken and shark show that this process does not have to be ordered, nor does it need to take place in two stages to generate a diverse repertoire and enable the expression of a single species of antigen receptor per cell, a restriction called allelic exclusion.

Autoreactivity and the positive selection of B cells

This review outlines the important role of autoreactivity in early B‐cell development and presents potential models for the regulation of the activation of peripheral B cells by different forms of self or foreign antigens.

V(D)J Recombination Exploits DNA Damage Responses to Promote Immunity.

Studies of B cell development and V(D)J recombination

The adaptation of next generation sequencing techniques to antigen receptor repertoire quantification has provided an unprecedented insight into repertoire diversity and the alterations it undergoes during infection or ageing.

Mechanisms of central tolerance for B cells

Mechanistic studies have begun to elucidate how divergent mechanisms that regulate tolerance are controlled, and single-cell antibody cloning has revealed defects of B cell central tolerance in human autoimmune diseases and in several human immunodeficiency diseases caused by single gene mutations.

Self-nonself Recognition through B-Cell Antigen Receptor

It is miraculous that only a few genes generate a repertoire of receptors that match essentially all of the molecular structures existing on earth including even newly generated chemical compounds, and amazing that each of the enormous number of receptors recognizes almost single specific structure.



Antigen receptor selection by editing or downregulation of V(D)J recombination.

Receptor editing in self-reactive bone marrow B cells

In mice transgenic for anti-H-2Kk,b antibody genes, in which a homogeneous clone of developing B cells can be analyzed for the outcome of autoantigen encounter, surface immunoglobulin M+/idiotype+ immature B cells binding to self-antigens in the bone marrow are induced to alter the specificity of their antigen receptors.

Receptor selection in B and T lymphocytes.

The immune system takes advantage of its control of V(D)J recombination to modify antigen receptors in such a way that self/non-self discrimination is enhanced.

Receptor editing is the main mechanism of B cell tolerance toward membrane antigens

It is shown that tolerance toward a membrane antigen–reactive B cell clone acts by receptor editing with very minimal cell loss, and suggests that clonal deletion is a default pathway that functions only when receptor editing has been exhausted.

T cell receptor gene recombination patterns and mechanisms: cell death, rescue, and T cell production

The results show that T cell production efficiency is enhanced through rearrangement of TCR-beta chain genes early during T cell development, with selective expansion of those cells possessing in-frame rearrangements, and strict correlations between successful T CR-beta gene rearrangEMENT, the onset of Tcr-alpha gene rearranged, rapid cell division, and programmed cell death, which together serve to maintain cell turnover and homeostasis during Tcell development.

Receptor editing in developing T cells

Transgenic mice that expressed a peptide antigen in the cortical epithelial cells of the thymus caused T cell receptor (TCR) internalization and increased gene rearrangement at the endogenous TCRα locus, or receptor editing.

Editors and editing of anti-DNA receptors.

B cell receptor expression level determines the fate of developing B lymphocytes: receptor editing versus selection.

A significant role of developmental block and receptor editing in B cell receptor quality control is demonstrated and both underexpressed and harmful B cell receptors can undergo correction by receptor editing.