Self-antigen does not accelerate immature B cell apoptosis, but stimulates receptor editing as a consequence of developmental arrest

Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9267-72. doi: 10.1073/pnas.94.17.9267.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Autoantigens / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology*
  • Cell Differentiation / immunology
  • Immune Tolerance
  • Mice
  • Receptors, Antigen, B-Cell / immunology*

Substances

  • Autoantigens
  • Receptors, Antigen, B-Cell