RAG-mediated secondary rearrangements of B-cell antigen receptors in rheumatoid synovial tissue

Autoimmun Rev. 2007 Dec;7(2):155-9. doi: 10.1016/j.autrev.2007.02.011. Epub 2007 Mar 21.

Abstract

Rheumatoid arthritis (RA) induces major changes in synovial tissue (ST) and cartilage and bone destruction. Still, its pathogenesis is poorly understood. Accumulating evidence points to an important role for B lymphocytes. Rheumatoid-ST is characterized by activation of the synoviocytes and infiltrated by various inflammatory cells such as B and T lymphocytes. The infiltrate is diffuse or organized as germinal centers (GCs). These accommodate the immune response and favor self-tolerance breakdown. Receptor revision in B cells results from re-expression of the recombination activating genes (RAGs) which reinitiate immunoglobulin gene recombination, and modify the B-cell antigen receptor accordingly. In rheumatoid ST, secondary VDJ rearrangements occur and RAG proteins are detected. The mechanism that triggers and controls this revision remains elusive. We favor the hypothesis that such an uncontrolled process leads to autoimmunity.

Publication types

  • Review

MeSH terms

  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism
  • Autoimmunity
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cytokines / immunology
  • Cytokines / metabolism
  • DNA-Binding Proteins / metabolism
  • Gene Rearrangement, B-Lymphocyte
  • Genes, Immunoglobulin
  • Genes, RAG-1*
  • Germinal Center / immunology*
  • Germinal Center / metabolism
  • Homeodomain Proteins / metabolism
  • Humans
  • Nuclear Proteins / metabolism
  • Receptors, Antigen, B-Cell / immunology*
  • Receptors, Antigen, B-Cell / metabolism
  • Recombination, Genetic / genetics
  • Synovial Membrane / immunology*
  • Synovial Membrane / metabolism

Substances

  • Cytokines
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Nuclear Proteins
  • RAG2 protein, human
  • Receptors, Antigen, B-Cell
  • RAG-1 protein