In vitro synthesis of immunoglobulins and IgM-rheumatoid factor by blood mononuclear cells of patients with rheumatoid arthritis

Abstract

In vitro synthesis of IgG, IgM and IgM-rheumatoid factor (IgM-RF) was investigated in unstimulated and pokeweed mitogen (PWM)-stimulated 7-day cultures of blood mononuclear cells (BMC) from 28 seropositive patients with active rheumatoid arthritis (RA), in a second group of 13-day cultures from 94 unselected rheumatoid patients, and in 21 healthy controls. Both normal and rheumatoid BMC cultures synthesized IgM-RF in response to PWM stimulation. Mitogen-induced stimulation was shown to be dependent on the presence of T-lymphocytes. PWM-induced IgM and IgM-RF synthesis were reduced in BMC from rheumatoid patients in comparison with healthy controls. However, the fraction of IgM-RF in the total IgM synthesized was significantly higher in the RA supernatants than in the controls, suggesting the presence of a larger precursor B-cell population committed to IgM-RF synthesis in those cultures. BMC from 44 of the 94 patients demonstrated spontaneous synthesis of IgM-RF, and this was positively correlated with disease activity and rheumatoid factor titer. Spontaneous production was shown to reside in the T-lymphocyte depleted, adherent cell-depleted, B-cell subpopulation. It is concluded that in active RA there is a specific activation and expansion of the circulating B-cell subpopulation committed to IgM-RF synthesis, possibly due to abnormal immunoregulatory mechanisms modulating synthesis of this antibody.