Fibroblast-like synoviocytes support B-cell pseudoemperipolesis via a stromal cell-derived factor-1- and CD106 (VCAM-1)-dependent mechanism

J Clin Invest. 2001 Feb;107(3):305-15. doi: 10.1172/JCI11092.


B-cell accumulation and formation of ectopic germinal centers are characteristic changes in the diseased joints of patients with rheumatoid arthritis (RA). Earlier studies suggested that interactions between B lymphocytes and specialized synovial "nurse-like" cells peculiar to the RA synovium may be responsible for the homing and sustained survival of B cells in the synovium. However, in this study, we found that B cells spontaneously migrate beneath ordinary fibroblast-like synoviocytes (FLSs) and then experience prolonged survival. FLSs isolated from joints of patients with osteoarthritis also supported this activity, termed B-cell pseudoemperipolesis. We found that FLSs constitutively expressed the chemokine stromal cell-derived factor-1 (SDF-1), and that pertussis toxin or antibodies to the SDF-1 receptor (CXCR4) could inhibit B-cell pseudoemperipolesis. However, expression of SDF-1 is not sufficient, as dermal fibroblasts also expressed this chemokine but were unable to support B-cell pseudoemperipolesis unless previously stimulated with IL-4 to express CD106 (VCAM-1), a ligand for the alpha(4)beta(1) integrin, very-late-antigen-4 (VLA-4 or CD49d). Furthermore, mAb's specific for CD49d and CD106, or the synthetic CS1 fibronectin peptide, could inhibit B-cell pseudoemperipolesis. We conclude that ordinary FLSs can support B-cell pseudoemperipolesis via a mechanism dependent upon fibroblast expression of SDF-1 and CD106.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arthritis, Rheumatoid / metabolism
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / physiology*
  • Cell Line
  • Cell Membrane Permeability
  • Chemokine CXCL12
  • Chemokines, CXC / metabolism
  • Chemokines, CXC / pharmacology
  • Fibroblasts / drug effects
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Integrin alpha4beta1
  • Integrins / metabolism
  • Interleukin-4 / pharmacology
  • Membrane Potentials
  • Receptors, Lymphocyte Homing / metabolism
  • Skin / metabolism
  • Stromal Cells / metabolism*
  • Synovial Membrane / cytology
  • Synovial Membrane / physiology*
  • Vascular Cell Adhesion Molecule-1 / biosynthesis


  • CXCL12 protein, human
  • Chemokine CXCL12
  • Chemokines, CXC
  • Integrin alpha4beta1
  • Integrins
  • Receptors, Lymphocyte Homing
  • Vascular Cell Adhesion Molecule-1
  • Interleukin-4