B lymphocyte function in patients with rheumatoid arthritis: impact of regulatory T lymphocytes and macrophages--modulation by antirheumatic drugs.

The present work analyses B lymphocyte functions in vitro in patients with rheumatoid arthritis (RA). The impact of gold salts and penicillamine on human B lymphocyte function in vitro is discussed. Synovial fluid monocytes/macrophages increased both the polyclonally induced and the antigen-induced blood lymphocyte proliferation and increased the numbers of immunoglobulin-secreting blood B lymphocytes generated by pokeweed mitogen (PWM), a T cell-dependent polyclonal activator. The lymphostimulatory factor(s) interleukin-1, which can be produced by monocytes/macrophages, was found in most cell-free synovial fluid specimens, but only in a few paired serum samples. Thus, in vivo activated synovial monocytes/macrophages may modulate lymphocyte functions. Compared to blood, synovial fluid T lymphocytes comprised fewer T4+ (helper/inducer) cells and more T8+ (suppressor/cytotoxic) cells. Synovial fluid lymphocytes proliferated poorly when stimulated polyclonally. However, the proliferative responses to microbial antigens as well as the lectin-induced lymphokine production equaled those of blood lymphocytes. In about half of RA patients, T4+ cells from synovial fluid increased the PWM-induced immunoglobulin secretion by autologous blood B lymphocytes to higher levels as compared to similar experiments with blood T4+ cells. Synovial fluid T8+ cells suppressed PWM-induced immunoglobulin production of autologous mononuclear cells to the same degree as seen with blood T8+ cells. A large proportion of synovial fluid T subsets expressed Ia antigens, probably due to in vivo activation. Thus, synovial T helper/inducer and T suppressor/cytotoxic cells may modulate the functional activities of synovial B lymphocytes. Among mononuclear cells isolated from synovial fluid and synovial tissue, considerable numbers of B lymphocytes spontaneously secreting IgG were found; fewer B cells secreted IgM and IgA. Rheumatoid factor activity was noted in about 7% of the IgG-producing cells. Synovial fluid mononuclear cells did not produce immunoglobulins in cultures stimulated with PWM, unless synovial T cells were removed and replaced with autologous blood T cells. Under these conditions synovial fluid B lymphocytes were induced by PWM to considerable IgG synthesis; fewer cells secreted IgM and IgA. About 8-9% of the induced IgM- and IgG-synthesizing cells displayed rheumatoid factor activity. Aurothiomalate markedly inhibited PWM-induced immunoglobulin production by normal lymphocytes cultured in vitro, probably by affecting monocyte/macrophage-lymphocyte interactions. The drug also had a direct inhibitory action on B lymphocytes, whereas T cells were resistant.(ABSTRACT TRUNCATED AT 400 WORDS)