Nurse-like cells from bone marrow and synovium of patients with rheumatoid arthritis promote survival and enhance function of human B cells

J Clin Invest. 1998 Aug 1;102(3):606-18. doi: 10.1172/JCI3162.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibody Formation
  • Antigens, CD / analysis
  • Apoptosis
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / pathology*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology*
  • Bone Marrow Cells / pathology
  • Bone Marrow Cells / physiology*
  • Cell Line, Transformed
  • Cell Survival
  • Cell Transformation, Viral
  • Cells, Cultured
  • Clone Cells
  • Coculture Techniques
  • Cytokines / analysis
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Cytokines / metabolism
  • Fibroblasts
  • HLA Antigens / analysis
  • Herpesvirus 4, Human
  • Humans
  • Immunophenotyping
  • Lymphocyte Activation
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Synovial Membrane / pathology
  • Synovial Membrane / physiology*

Substances

  • Antigens, CD
  • Cytokines
  • HLA Antigens
  • RNA, Messenger