During the T cell development the postulates is that if a developing thymocyte encounters self-antigen, it is induced to die via apoptosis, thereby protecting the organism from autoreactive T cells.
The antigen presentation by epithelial cells caused T cell receptor (TCR) internalization and increased gene rearrangement at the endogenous TCR alpha locus, or receptor editing. This editing mechanism in immature T cells parallels that which occurs in immature B cells, and has important implications for understanding positive and negative selection signaling in the thymus, and the limits of self-tolerance.
Self-reactive B cells specific for ubiquitous membrane-bound autoantigens are eliminated in the bone marrow by two mechanisms of tolerance: receptor editing and clonal deletion.
Acquired immunity relies upon a prolific but non-discriminating mechanism to generate an Ag receptor repertoire of innumerable specificities with the investment of a minimal amount of the genome's coding capacity. This strategy, however, requires a mechanism to address the generation of lymphocytes whose Ag receptors recognize self molecules.
However, the relative contributions of clonal deletion and receptor editing to B cell tolerance in a polyclonal B cell population have not been established. Here we show that tolerance toward a membrane antigen-reactive B cell clone acts by receptor editing with very minimal cell loss. The capacity of receptor editing to rescue almost all autoreactive B cells from deletion relies on the availability of multiple joining light chain gene segments as substrate for secondary immunoglobulin light chain gene rearrangement and is independent of the affinity of the autoantigen and the presence of non-autoreactive B cells.
Graphical view of receptor editing
Receptor editing
The antigen presentation by epithelial cells caused T cell receptor (TCR) internalization and increased gene rearrangement at the endogenous TCR alpha locus, or receptor editing. This editing mechanism in immature T cells parallels that which occurs in immature B cells, and has important implications for understanding positive and negative selection signaling in the thymus, and the limits of self-tolerance.
Self-reactive B cells specific for ubiquitous membrane-bound autoantigens are eliminated in the bone marrow by two mechanisms of tolerance: receptor editing and clonal deletion.
Acquired immunity relies upon a prolific but non-discriminating mechanism to generate an Ag receptor repertoire of innumerable specificities with the investment of a minimal amount of the genome's coding capacity. This strategy, however, requires a mechanism to address the generation of lymphocytes whose Ag receptors recognize self molecules.
However, the relative contributions of clonal deletion and receptor editing to B cell tolerance in a polyclonal B cell population have not been established. Here we show that tolerance toward a membrane antigen-reactive B cell clone acts by receptor editing with very minimal cell loss. The capacity of receptor editing to rescue almost all autoreactive B cells from deletion relies on the availability of multiple joining light chain gene segments as substrate for secondary immunoglobulin light chain gene rearrangement and is independent of the affinity of the autoantigen and the presence of non-autoreactive B cells.
Graphical view of receptor editing
Receptor editing
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| B-cell and T cell receptor editing |
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