Regulation of synovial B cell survival in rheumatoid arthritis by vascular cell adhesion molecule 1 (CD106) expressed on fibroblast-like synoviocytes.
OBJECTIVE
B lymphocytes accumulate in the inflamed joints of patients with rheumatoid arthritis (RA) and are responsible for production of high amounts of (auto)-antibodies. The aim of this study was to determine the capacity of fibroblast-like synoviocytes (FLS) to contribute to the accumulation of synovial fluid (SF) B cells by extending their life span.


METHODS
Highly purified SF B cells were cultured with FLS in the presence or absence of blocking antibodies directed against cell adhesion molecules, and cell viability was determined after various time intervals by trypan blue, annexin V, propidium iodide, or Hoechst staining. Phenotypic characterization of peripheral blood and SF B cells and FLS was carried out by flow cytometry.


RESULTS
Synovial B cells, which consist predominantly of memory B cells and plasma cells (PC), undergo spontaneous cell death by apoptosis upon removal from their in vivo environment, despite expression of Bcl-2. Coculture with FLS rescued synovial B cells from apoptosis in a cell contact-dependent manner. Blocking studies using monoclonal antibodies demonstrated a role for the molecular interaction of SF B cells with vascular cell adhesion molecule 1 (VCAM-1; CD106) in FLS-induced survival. The ability of FLS to induce SF B cell survival was not related to the rheumatoid origin since FLS from non-RA patients had similar properties.


CONCLUSIONS
These findings indicate a crucial role for FLS in the survival of synovial B cells at the site of inflammation in RA through the interaction with VCAM-1 expressed on FLS. Consequently, memory B cells and PC accumulation arise and persist not only as a result of maturation and recruitment of these cells, but also by active prevention from cell death by the microenvironment.
Reparon-Schuijt
C C
CC
Leiden University Medical Center, The Netherlands.
van Esch
W J
WJ
van Kooten
C
C
Rozier
B C
BC
Levarht
E W
EW
Breedveld
F C
FC
Verweij
C L
CL
D019138:Antibodies, Blocking / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D001402:B-Lymphocytes / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D018920:Coculture Techniques; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D013582:Synovial Fluid / Q000166:cytology; D013583:Synovial Membrane / Q000166:cytology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000276:immunology
D019138:Antibodies, Blocking; D015815:Cell Adhesion Molecules; D019010:Vascular Cell Adhesion Molecule-1