RAG-mediated secondary rearrangements of B-cell antigen receptors in rheumatoid synovial tissue.
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.
Laboratory of Immunology, Brest University Medical School Hospital, BP 824, F 29609 Brest, France.
Caroline
C
Rochas
Sophie
S
Hillion
Pierre
P
Youinou
Christophe
C
Jamin
Valérie
V
Devauchelle-Pensec
D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D016654:Genes, RAG-1; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D011995:Recombination, Genetic / Q000235:genetics; D013583:Synovial Membrane / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D011947:Receptors, Antigen, B-Cell; C064658:RAG-1 protein