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. CONCLUSION: In patients with RA, circulating B cells capable of spontaneous IgM-RF secretion require IL-10 production by adherent cells to reach terminal maturation.
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. CONCLUSION: 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: Y Chernajovsky; A Annenkov; C Herman; K Triantaphyllopoulos; D Gould; H Dreja; S P Moyes; J L Croxford; R A Mageed; O L Podhajcer; D Baker Journal: Drugs Aging Date: 1998-01 Impact factor: 3.923
Authors: J Eskdale; G Gallagher; C L Verweij; V Keijsers; R G Westendorp; T W Huizinga Journal: Proc Natl Acad Sci U S A Date: 1998-08-04 Impact factor: 11.205
Authors: H Schotte; B Schlüter; S Drynda; P Willeke; N Tidow; G Assmann; W Domschke; J Kekow; M Gaubitz Journal: Ann Rheum Dis Date: 2004-09-02 Impact factor: 19.103