Lymphoid neogenesis in rheumatoid synovitis

S. Takemura, A. Braun, C. Crowson, P. J. Kurtin, R. H. Cofield, W. M. O'Fallon, J. J. Goronzy, C. M. Weyand

Research output: Contribution to journalArticle

501 Scopus citations

Abstract

In rheumatoid arthritis (RA), tissue-infiltrating lymphocytes can be arranged in sophisticated organizations that resemble microstructures usually formed in secondary lymphoid organs. Molecular pathways and host risk factors involved in this process of lymphoid neogenesis remain to be defined. In a series of 64 synovial tissue biopsies, lymphoid follicles with germinal centers (GCs) were found in 23.4% of the patients. Follicular dendritic cells (FDCs) were exclusively present in tissues with GCs, suggesting that the recruitment or in situ maturation of FDCs is a critical factor for GC formation in the synovial membrane. Primary follicles were absent, emphasizing the role of Ag recognition in the generation of inflammation-associated lymphoid organogenesis. Multivariate logistic regression analysis of tissue cytokines and chemokines identified two parameters, in situ transcription of lymphotoxin (LT)-β and of B lymphocyte chemoattractant (BLC; BLC/CXCL13), that were predictors for FDC recruitment and synovial GC formation. LT-β and BLC/CXCL13 were found to be independent variables that could, in part, compensate for each other to facilitate GC formation. Prediction models incorporating in situ transcription of LT-β and BLC/CXCL13 had high negative yet moderate positive predictive values, suggesting that LT-β and BLC/CXCL13 are necessary but not sufficient. LT-β protein was detected on a subset of mantle zone and GC B cells, but also on T cells in follicular structures. BLC/CXCL13 was produced by FDCs in follicular centers, but was predominantly found in endothelial cells and synovial fibroblasts, suggesting heterotypic signaling between cells of the synovial membrane and infiltrating lymphocytes in regulating extranodal lymphoid neogenesis.

Original languageEnglish (US)
Pages (from-to)1072-1080
Number of pages9
JournalJournal of Immunology
Volume167
Issue number2
DOIs
StatePublished - Jul 15 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Takemura, S., Braun, A., Crowson, C., Kurtin, P. J., Cofield, R. H., O'Fallon, W. M., Goronzy, J. J., & Weyand, C. M. (2001). Lymphoid neogenesis in rheumatoid synovitis. Journal of Immunology, 167(2), 1072-1080. https://doi.org/10.4049/jimmunol.167.2.1072