Evidence for an antigen-driven immune response in the chronically inflamed synovium

  • Claudia Bearek1 and

    Affiliated with

    • H-J Kim1

      Affiliated with

      Arthritis Res19991(Suppl 1):S09

      DOI: 10.1186/ar23

      Published: 15 November 1999

      Full text

      Recently it has been shown that proinflammatory cytokines, like TNF-alpha and lymphotoxin play a crucial role in the organogenesis of the lymphoid tissue. Thus, during chronic inflammation, in the affected tissue, these cytokines may promote the development of a micro-environment which supports a local immune response. In patients with rheumatoid arthritis large lymphocytic infiltrates are often seen in the synovial tissue. These cell clusters have a characteristic arrangement of T, B and plasma cells. Proliferating B cells are found only centrally in a network of follicular dendritic cells. Using micro-manipulation CD20+ B cells and plasma cells were isolated separately from different parts of single infiltrates. DNA was extracted and the VH/VL gene repertoires determined. The data show that within the network of follicular dendritic cells there is an oligoclonal expansion of B cells. During proliferation V-gene variants are generated by the hypermutation mechanism. The pattern of somatic mutations suggests that both naive and memory B cells become activated in the synovial tissue. Within single infiltrates we did not find identical rearrangements between CD20+ B and plasma cells. Nevertheless, the finding of clonally related plasma cells suggests that these cells underwent terminal differentiation in the synovial tissue. The analysis of individual B cells recovered from synovial tissue opens a new way to determine the specificity of those cells which take part in the local immune reaction.

      Authors’ Affiliations

      (1)
      Deutsches Rheuma ForschungsZentrum

      References

      1. Berek C, Kim H-J: B-cell activation and development within chronically inflamed synovium in rheumatoid and reactive arthritis. Sem Immunol 1997, 9:261–268.View Article
      2. Fu Y-X, Chaplin DD: Development and maturation of secondary lymphoid organs. Annu Rev Immunol 1999, 17:399–433.View ArticlePubMed
      3. Kim H-J, Krenn V, Steinhauser G, Berek C: Plasma cell development in synovial germinal centers in patients with rheumatoid and reactive arthritis. J Immunol 1999, 162:3053–3062.PubMed
      4. Randen I, Mellbye J, Forre O, Natvig JB: The identification of germinal centres and follicular dendritic networks in rheumatoid synovial tissue. Scand J Immuol 1995, 41:481–486.View Article
      5. Schröder AE, Greiner A, Seyfert C, Berek C: Differentiation of B cells in the nonlymphoid tissue of the synovial membrane of patients with rheumatoid arthritis. Proc Natl Acad Sci USA 1996, 93:221–225.View ArticlePubMed

      Copyright

      © Current Science Ltd 2000

      Advertisement