Abstract
Bcl-xl and plasma cell survival in rheumatoid synovium
Full text
S Busteed, MW Bennett, M Stone, C Molloy, J O’Connell, F Shanahan, MG MolloyMedicine
Rheumatology, Toronto Western Hospital, Toronto, Canada
Rheumatology, Cork University Hospital, Cork, IrelandBackground
Bcl-xL is a Bcl-2 homologue that regulates lymphocyte apoptosis. It has been reported that co-culture of B cells with rheumatoid synovial stromal cells induces upregulation of Bcl-xL, consequently inhibiting B cell apoptosis. Impaired apoptosis of auto-antibody producing B cells may contribute to the perpetuation of inflammation in rheumatoid arthritis (RA). The phenotype of synovial T lymphocytes in RA – Bcl-xL
/Bcl-2
, may also be linked to the enhanced survival of T lymphocytes within the joint.
Objectives
In this study, we examined the expression of Bcl-xL in rheumatoid synovium using immunohistochemistry.
Methods
Sections of synovium were obtained intraoperatively from patients with RA (n = 18). Specimens from patients with osteoarthritis were used as non-inflammatory controls (n = 9). Staining was carried out using a polyclonal rabbit antibody to Bcl-xL. Peripheral blood lymphocytes were used as positive biological controls. Detection of cell death was carried out using the TUNEL assay (terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick end labelling). Identification of plasma cells within the lymphocyte population was performed using a monoclonal antibody to CD138.
Results
Bcl-xL was expressed in both RA and OA tissue. Of note, there was a marked infiltrate of Bcl-xL positive cells in 13 of the 18 RA sections with scattered positive cells in a further 2 sections. Only 1 of the 9 OA sections demonstrated a similar degree of plasma cell infiltration and Bcl-xL expression, although a few positive plasma cells were noted in the remaining sections. Plasma cells infiltrates that were Bcl-xL positive were noted to be TUNEL-negative on consecutive sections.
Conclusion
Upregulation of Bcl-xL by plasma cells in rheumatoid synovium may prevent their elimination by apoptosis and may play a role in the pathogenesis in rheumatoid arthritis.
Citation: Ann Rheum Dis, volume 60, supplement 1, year 2001, page A394Session: Cartilage in bone biology and pathophysiology
3 organizations
Organization
Medicine, Kuopio University Hospital, Kuopio