Igkappa allelic inclusion is a consequence of receptor editing

J Exp Med. 2007 Jan 22;204(1):153-60. doi: 10.1084/jem.20061918. Epub 2007 Jan 8.

Abstract

The discovery of lymphocytes bearing two light chains in mice carrying self-reactive antibody transgenes has challenged the "one lymphocyte-one antibody" rule. However, the extent and nature of allelically included cells in normal mice is unknown. We show that 10% of mature B cells coexpress both Igkappa alleles. These cells are not the result of failure in allelic exclusion per se, but arise through receptor editing. We find that under physiological conditions, editing occurs both by deletion and by inclusion with equal probability. In addition, we demonstrate that B lymphocytes carrying two B-cell receptors are recruited to germinal center reactions, and thus fully participate in humoral immune responses. Our data measure the scope of allelic inclusion and provide a mechanism whereby autoreactive B cells might "escape" central tolerance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Alleles
  • Animals
  • Antibody Diversity
  • Antigenic Variation
  • Autoimmunity
  • B-Lymphocytes / immunology
  • Base Sequence
  • DNA Primers / genetics
  • Gene Expression
  • Gene Rearrangement, B-Lymphocyte, Light Chain
  • Immunoglobulin kappa-Chains / genetics*
  • In Vitro Techniques
  • Mice
  • Models, Immunological
  • RNA Editing
  • Receptors, Antigen, B-Cell / genetics
  • Self Tolerance

Substances

  • DNA Primers
  • Immunoglobulin kappa-Chains
  • Receptors, Antigen, B-Cell