SELECTIVE INDUCTION OF IGM RHEUMATOID FACTORS BY CD14-LINEAGE CELLS GENERATED FROM BONE-MARROW OF PATIENTS WITH RHEUMATOID-ARTHRITIS( MONOCYTE)

Objective. To determine the capacity of CD14+ monocyte-lineage cells i nduced from bone marrow of rheumatoid arthritis (RA) patients to stimu late the production of IgM rheumatoid factor (IgM-RF), in order to exp lore the functional abnormalities of CD14+ cells and gain insight into the mechanism of selective synthesis of IgM-RF in RA. Methods. CD14cells were induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation of CD14- cells purified from bone marrow cells o btained from 6 RA patients and 6 osteoarthritis (OA) patients. The pro duction of IgM and IgM-RF was induced by stimulating B cells from norm al healthy individuals with immobilized anti-CD3-activated autologous CD4+ T cells. The effects of CD14+ cells on the proportion of IgM-RF t o total IgM produced by the normal B cells were assessed, Results. CD1 4+ cells induced by GM-CSF stimulation of bone marrow CD14- cells from the 6 RA patients significantly enhanced the proportion of IgM-RF to total IgM produced by anti-CD3-activated CD4+ T cell-stimulated normal B cells (P < 0.05), whereas GM-CSF-induced CD14+ cells from the bone marrow of the 6 OA patients did not significantly affect IgM-RF produc tion, CD14+ cells induced by GM-CSF obtained from different sites in t he same RA patient on different occasions consistently enhanced the pr oportion of IgM-RF to IgM produced by B cells from different normal su bjects. Conclusion. These results indicate that abnormal CD14+ monocyt es stimulate RF-producing B cells to be ready to be activated by the s ignals delivered through noncognate T-B interactions with anti-CD3-act ivated T helper cells. Moreover, the data suggest that the accelerated generation of such functionally abnormal CD14+ cells from bone marrow precursors might play an important role in the pathogenesis of RA.