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, especial ly at extralymphoid sites. To address this issue, nurse-like cell clon es from bone marrow and synovial tissue of patients with RA (RA-NLC) w ere established and characterized. RA-NLC constitutively expressed CD2 9, CD49c, CD54 (ICAM-1), CD106 (VCAM-1), CD157 (BST-1), and class I MH C molecules, and secreted IL-6, IL-7, IL-8, granulocyte-macrophage col ony-stimulating factor (GM-CSF) and granulocyte colony-stimulating fac tor (G-CSF). Bone marrow-derived and synovial RA-NLC differed in that the former secreted IL-7 and expressed a greater density of CD157 cons titutively and after stimulation with IFN gamma, whereas the latter se creted G-CSF and more IL-6. Stimulation of both bone marrow and synovi al RA-NLC induced expression of CD40 and class II MHC, but not CD154 ( CD40L) or CD35. RA-NLC rescued peripheral B cells from spontaneous apo ptosis and promoted survival of B cells for > 4 wk. B cell survival wa s blocked by antibodies to CD106 or CD157. RA-NLC also increased Ig pr oduction from B cells. After long-term culture (4-6 wk) with RA-NLC, b ut not alone or with fibroblasts, outgrowth of B cells was observed. A ll B cell lines derived from these cultures had been transformed by EB V, although the RA-NLC themselves were not infected with EBV, Precurso r frequency analysis indicated that similar to 1 in 12,500 peripheral B cells could give rise to these EBV-transformed B cell lines upon coc ulture with RA-NLC. These results indicate that RA-NLC from bone marro w and synovium have the capacity to rescue B cells from spontaneous ap optosis, facilitate Ig production, and promote the outgrowth of EBV-tr ansformed B lymphoblastoid cells. These findings suggest that RA-NLC m ay play a role in the local and systemic hyperreactivity of B cells ch aracteristic of rheumatoid arthritis.