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

Objective. To determine the capacity of CD14+ monocyte-lineage cells induced from bone marrow of rheumatoid arthritis (RA) patients to stimulate the production of IgM rheumatoid factor (IgM-RF), in order to explore the functional abnormalities of CD14+ cells and gain insight into the mechanism of selective synthesis of IgM-RF in RA. Methods. CD14+ cells were induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation of CD14- cells purified from bone marrow cells obtained from 6 RA patients and 6 osteoarthritis (OA) patients. The production of IgM and IgM-RF was induced by stimulating B cells from normal healthy individuals with immobilized anti-CD3-activated autologous CD4+ T cells. The effects of CD14+ cells on the proportion of IgM-RF to total IgM produced by the normal B cells were assessed, Results. CD14+ 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 production, CD14+ cells induced by GM-CSF obtained from different sites in the same RA patient on different occasions consistently enhanced the proportion of IgM-RF to IgM produced by B cells from different normal subjects. Conclusion. These results indicate that abnormal CD14+ monocytes stimulate RF-producing B cells to be ready to be activated by the signals delivered through noncognate T-B interactions with anti-CD3-activated 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.