title: Terminal differentiation of spontaneous rheumatoid factor-secreting B cells from rheumatoid arthritis patients depends on endogenous interleukin-10.
abstract: OBJECTIVE
  The presence of serum rheumatoid factor (RF) and spontaneous RF-secreting B cells is a common feature in most patients with rheumatoid arthritis (RA). This study analyzed the cytokine(s) that controls the final maturation of B cells capable of spontaneous IgM-RF secretion in vitro.
  
  
  METHODS
  RA patients' peripheral blood mononuclear cells (PBMC), as well as adherent and nonadherent cell fractions, were cultured, and spontaneous IgM-RF and interleukin-10 (IL-10) secretion were determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The RF+ RA PBMC, but not PBMC from RF- RA patients or healthy controls, actively produced IgM-RF in a linear manner for 14 days. This activity depended on the presence of fetal calf serum and did not require cellular DNA synthesis. Spontaneous IgM-RF secretion depended on IL-10, as deduced from the following findings: 1) IL-10, but not a variety of cytokines including IL-6, restored missing IgM-RF secretion by PBMC in serum-free supplemented cultures; 2) the addition of anti-IL-10, but not anti-IL-6, blocking antibodies inhibited PBMC IgM-RF secretion, and this effect could be reversed by exogenous IL-10; and 3) RA PBMC actively produced IL-10 in vitro. The cells responsible for endogenous IL-10 production were found in the adherent cell fraction. Finally, IL-10 induced IgM-RF, but not total IgM, secretion by RA PBMC.
  
  
  CONCLUSIONS
  In patients with RA, circulating B cells capable of spontaneous IgM-RF secretion require IL-10 production by adherent cells to reach terminal maturation.
authors.affiliation: Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Perez
authors.forename: J
authors.initials: J
authors.lastname: Orte
authors.forename: J A
authors.initials: JA
authors.lastname: Brieva
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002454:Cell Differentiation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000502:physiology*; D012217:Rheumatoid Factor / Q000378:metabolism*
chemical_list: D007075:Immunoglobulin M; D016753:Interleukin-10; D012217:Rheumatoid Factor