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 stromal cell line (SCL) derived from RA synovial tissue, and the effects on apoptosis and expression of Bcl-2-related proteins were analyzed. As a control, 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-xL 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-xL 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-xL expression. These results indicate that SCL derived from RA synovial tissue play a role in promoting B cell survival by inducing Bcl-xL expression and blocking B cell apoptosis in a CD49d/CD29-CD106-dependent manner.
Hayashida
K
K
University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
Shimaoka
Y
Y
Ochi
T
T
Lipsky
P E
PE
D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology*; D016023:Integrins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D038981:Receptors, Collagen; D017154:Stromal Cells / Q000276:immunology / Q000473:pathology; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology*; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D019012:Integrin beta1; D016023:Integrins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D038981:Receptors, Collagen; D019010:Vascular Cell Adhesion Molecule-1; D051020:bcl-X Protein