RS rearrangement frequency as a marker of receptor editing in lupus and type 1 diabetes

J Exp Med. 2008 Dec 22;205(13):2985-94. doi: 10.1084/jem.20082053. Epub 2008 Dec 15.

Abstract

Continued antibody gene rearrangement, termed receptor editing, is an important mechanism of central B cell tolerance that may be defective in some autoimmune individuals. We describe a quantitative assay for recombining sequence (RS) rearrangement that we use to estimate levels of antibody light chain receptor editing in various B cell populations. RS rearrangement is a recombination of a noncoding gene segment in the kappa antibody light chain locus. RS rearrangement levels are highest in the most highly edited B cells, and are inappropriately low in autoimmune mouse models of systemic lupus erythematosus (SLE) and type 1 diabetes (T1D), including those without overt disease. Low RS rearrangement levels are also observed in human subjects with SLE or T1D.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Autoimmunity / physiology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / physiology
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / metabolism
  • Female
  • Gene Rearrangement, B-Lymphocyte, Light Chain*
  • Genes, Immunoglobulin
  • Genetic Markers*
  • Humans
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / metabolism
  • Lymphocyte Subsets
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Middle Aged
  • Young Adult

Substances

  • Genetic Markers