Human IgG aggregates induce selective stimulation of IgM rheumatoid factor synthesis by rheumatoid blood mononuclear...

Peripheral blood mononuclear cells (PBM) from patients with active rheumatoid arthritis (RA) contain precursor B lymphocytes specific for IgM rheumatoid factor (IgM-RF) synthesis. In this study, human IgG aggregates (HaIgG) were used to stimulate monocyte-depleted PBM from 46 patients with RA and 21 normal controls. The cells were incubated with HaIgG and pokeweed mitogen for 72 hours, washed, and then cultured in microwells for an additional 11 days. HaIgG induced an increase in IgM-RF synthesis by RA cells with optimum response at 0.1 microgram/ml (P less than 0.001). Total IgM synthesis remained unchanged. In contrast, HaIgG did not stimulate IgM-RF production by normal cells. Specificity of the IgM-RF response was shown by the concomitantly increased IgM-RF/IgM ratios, while IgM anti-trinitrophenyl antibodies did not increase. Aggregation of the IgG was required for it to be an effective stimulus. The findings suggest that circulating immune complexes in RA patients may provide the stimulus for sustained production of IgM-RF in vivo.