Nurse-like cells from bone marrow and synovium of patients with rheumatoid arthritis promote survival and enhance function of human B cells.
Thymic nurse cells are known to interact with T cells and play a role in their functional maturation. However, the role of nurse cells in B cell maturation and differentiation is less well established, especially at extralymphoid sites. To address this issue, nurse-like cell clones from bone marrow and synovial tissue of patients with RA (RA-NLC) were established and characterized. RA-NLC constitutively expressed CD29, CD49c, CD54 (ICAM-1), CD106 (VCAM-1), CD157 (BST-1), and class I MHC molecules, and secreted IL-6, IL-7, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF). Bone marrow-derived and synovial RA-NLC differed in that the former secreted IL-7 and expressed a greater density of CD157 constitutively and after stimulation with IFNgamma, whereas the latter secreted G-CSF and more IL-6. Stimulation of both bone marrow and synovial RA-NLC induced expression of CD40 and class II MHC, but not CD154 (CD40L) or CD35. RA-NLC rescued peripheral B cells from spontaneous apoptosis and promoted survival of B cells for > 4 wk. B cell survival was blocked by antibodies to CD106 or CD157. RA-NLC also increased Ig production from B cells. After long-term culture (4-6 wk) with RA-NLC, but not alone or with fibroblasts, outgrowth of B cells was observed. All B cell lines derived from these cultures had been transformed by EBV, although the RA-NLC themselves were not infected with EBV. Precursor frequency analysis indicated that approximately 1 in 12,500 peripheral B cells could give rise to these EBV-transformed B cell lines upon coculture with RA-NLC. These results indicate that RA-NLC from bone marrow and synovium have the capacity to rescue B cells from spontaneous apoptosis, facilitate Ig production, and promote the outgrowth of EBV-transformed B lymphoblastoid cells. These findings suggest that RA-NLC may play a role in the local and systemic hyperreactivity of B cells characteristic of rheumatoid arthritis.
Shimaoka
Y
Y
Department of Orthopedic Surgery, Osaka University Medical School, 2-2, Yamada-oka, Suita, Osaka 565, Japan.
Attrep
J F
JF
Hirano
T
T
Ishihara
K
K
Suzuki
R
R
Toyosaki
T
T
Ochi
T
T
Lipsky
P E
PE
D000917:Antibody Formation; D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D001854:Bone Marrow Cells / Q000473:pathology / Q000502:physiology*; D002461:Cell Line, Transformed; D002470:Cell Survival; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002999:Clone Cells; D018920:Coculture Techniques; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts; D006680:HLA Antigens / Q000032:analysis; D004854:Herpesvirus 4, Human; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013583:Synovial Membrane / Q000473:pathology / Q000502:physiology*
D015703:Antigens, CD; D016207:Cytokines; D006680:HLA Antigens; D012333:RNA, Messenger