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 downregulation 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.