Rheumatoid arthritis synovial stromal cells inhibit apoptosis and up-regulate Bcl-xL expression by B cells in a CD49/CD29-CD106-dependent mechanism

Inflammatory sites, such as rheumatoid arthritis (RA) synovial tissue, contain large numbers of activated B cells and plasma cells. However, the mechanisms maintaining B cell viability and promoting their differentiation are not known, but interactions with stromal cells may play a role. To examine this, purified human peripheral B cells were cultured with a stomal cell line (SCL) derived from RA synovial tissue, and the effects on apoptosis and expression of Bcl-2-related proteins were analyzed. As a central, B cells were also cultured with SCL from osteoarthritis synovium or skin fibroblasts, B cells cultured with medium alone underwent spontaneous apoptosis, However, B cells cultured with RA SCL cells exhibited less apoptosis and greater viability, Although SCL from osteoarthritis synovium and skin fibroblasts also rescued B cells from apoptosis, they were less effective than RA SCL, B cell expression of Bcl-x(L) was markedly increased by RA SCL in a contact-dependent manner, whereas B cell expression of Bcl-2 was unaffected. Protection of B cells from apoptosis and up-regulation of Bcl-x(L) by RA SCL were both blocked by mAbs to CD106 (VCAM-1), but not CD54 (ICAM-1). Furthermore, cross-linking of CD49d/CD29 (very late Ag-4) on the surface of B cells rescued them from apoptosis and up-regulated Bcl-x(L) expression, These results indicate that SCL derived from RA synovial tissue play a role in promoting B cell survival by inducing Bcl-x(L) expression and blocking I) cell apoptosis in a CD49d/(CD29-CD106-dependent manner.