Expression and reexpression of recombination activating genes: relevance to the development of autoimmune states

Ann N Y Acad Sci. 2005 Jun:1050:10-8. doi: 10.1196/annals.1313.002.

Abstract

Like all antibodies, autoreactive antibodies are generated in developing B cells in the bone marrow by variable (V), diversity (D), and joining (J) recombination under the regulation of recombination activating gene (RAG) 1 and RAG2 proteins. Deletion, anergy, and receptor edition prevent the emergence of autoreactive B cells. In the periphery, somatic hypermutation during the course of germinal center responses can lead to the emergence of autoreactive and low-affinity antibody-producing B cells. Deletion and receptor revision regulate autoreactive and inappropriate B cells. Defects in central or peripheral tolerance mechanisms associated with RAG expression could contribute to the appearance of autoreactive B cells. We demonstrate the presence of RAG(+) B cells in CD5-expressing cells outside germinal centers. Our data suggest that receptor revision in the periphery also may occur in unusual sites when B cells are induced to express CD5. This revision may correspond to a novel regulation checkpoint in which impaired control of RAG expression could generate autoreactive B cells and lead to autoimmune states.

Publication types

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

MeSH terms

  • Animals
  • Autoimmunity / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / physiology
  • CD5 Antigens / immunology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • Gene Expression Regulation / immunology*
  • Genes, RAG-1
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / immunology*
  • Humans
  • Models, Immunological
  • Nuclear Proteins
  • Recombination, Genetic*

Substances

  • CD5 Antigens
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Nuclear Proteins
  • RAG2 protein, human
  • V(D)J recombination activating protein 2
  • RAG-1 protein