Self-antigen does not accelerate immature B cell apoptosis, but stimulates receptor editing as a consequence of developmental arrest.
In pre-B lymphocytes, productive rearrangement of Ig light chain genes allows assembly of the B cell receptor (BCR), which selectively promotes further developmental maturation through poorly defined transmembrane signaling events. Using a novel in vitro system to study immune tolerance during development, we find that BCR reactivity to auto-antigen blocks this positive selection, preventing down-regulation of light chain gene recombination and promoting secondary light chain gene rearrangements that often alter BCR specificity, a process called receptor editing. Under these experimental conditions, self-antigen induces secondary light chain gene rearrangements in at least two-thirds of autoreactive immature B cells, but fails to accelerate cell death at this stage. These data suggest that in these cells the mechanism of immune tolerance is receptor selection rather than clonal selection.
Melamed
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Department of Pediatrics, Division of Basic Sciences, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Nemazee
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D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D002454:Cell Differentiation / Q000276:immunology; D007108:Immune Tolerance; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*
D001324:Autoantigens; D011947:Receptors, Antigen, B-Cell