Spontaneous DNA synthesis in rheumatoid arthritis: evidence of enhanced circulating non-T-cell proliferation

3H-thymidine incorporation in cultures of peripheral blood mononuclear cells from patients with seropositive rheumatoid arthritis (RA) and healthy controls was measured in vitro in the absence of added stimulants. A significantly higher level of spontaneous DNA synthesis was found in cultures of mononuclear cells from patients with clinically active RA than from patients with inactive disease and normal controls. This activity was more apparent in 24-h cultures than in 72-h cultures. There was no correlation between DNA levels and IgM rheumatoid factor (RF) titres. When T- and non-T-cell populations were separated and cultured simultaneously with unfractionated cells, only non-T cells maintained high levels of DNA synthesis, and enrichment of surface membrane Ig+ (SmIg) cells was generally associated with enhancement of 3H-thymidine incorporation. Furthermore, no difference was found in spontaneous DNA synthesis between cultures either containing or depleted of phagocytic cells. Moreover, the addition of graded numbers of autologous monocytes to highly purified T- and non-T-cell populations did not alter the background DNA synthesis. Thus, endogenously activated cells in RA patients are neither T lymphocytes nor monocytes. A regulatory influence by monocytes could not be demonstrated. It is suggested that cells actively engaged in DNA synthesis in RA blood are non-T cells in origin, most probably B lymphocytes.