Mature antigen-experienced T helper cells synthesize and secrete the B cell chemoattractant CXCL13 in the inflammatory environment of the rheumatoid joint

Arthritis Rheum. 2008 Nov;58(11):3377-87. doi: 10.1002/art.23966.


Objective: Synovial B cells play a critical role in rheumatoid arthritis (RA), being involved in autoantibody synthesis, T cell activation, and cytokine production. CXCL13 is a B cell chemoattractant that is instrumental in synovial B cell organization; the regulatory determinants of CXCL13 in inflammation are poorly characterized. This study was undertaken to investigate the functional involvement of synovial T cells in the ectopic expression of CXCL13 in RA.

Methods: CXCL13 production and regulation were addressed using immunohistochemistry, in situ hybridization, quantitative polymerase chain reaction, multicolor flow cytometry, and enzyme-linked immunosorbent assay, by in situ-ex vivo analysis and in vitro functional assays with rheumatoid synovial tissue and primary cells.

Results: CXCL13 messenger RNA and protein expression and spontaneous CXCL13 secretion were detected in RA synovial fluid T cells but were not detected (or were detected only occasionally) in peripheral blood T cells. Analysis of tissue expression confirmed cytoplasm localization of CXCL13 in T lymphocytes infiltrating B cell follicles and small perivascular aggregates. Multicolor characterizations in synovial fluid demonstrated CXCL13 expression in antigen-experienced T helper cells, frequently characterized by terminal differentiation and the lack of the follicular helper T cell markers CXCR5 and BCL6 protein. In vitro functional assays revealed the enhancing effect of T cell receptor-CD28 engagement on CXCL13 production and secretion in primary cells.

Conclusion: Our findings define a new functional property of synovial T cells, demonstrating their active involvement in the local production of B cell chemoattractants, and support a direct contribution of the adaptive immune system and antigen-dependent signals in the mechanisms of B cell localization in RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens / immunology
  • Arthritis, Rheumatoid / immunology*
  • B-Lymphocytes / immunology
  • Chemokine CXCL13 / biosynthesis*
  • Chemokine CXCL13 / metabolism*
  • DNA-Binding Proteins / analysis
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Middle Aged
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-bcl-6
  • RNA, Messenger / analysis
  • Receptors, CXCR5 / analysis
  • Synovial Fluid / chemistry
  • Synovial Membrane / cytology
  • Synovial Membrane / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*


  • Antigens
  • BCL6 protein, human
  • CXCR5 protein, human
  • Chemokine CXCL13
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • RNA, Messenger
  • Receptors, CXCR5