B-cell proliferation and differentiation in systemic lupus erythematosus and mixed connective tissue disease

Abstract

Systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) are characterized by B-cell hyperactivity as manifested by spontaneous in vitro production of immunoglobulins (Ig), but pokeweed mitogen (PWM)-induced Ig synthesis of peripheral blood (PB) mononuclear cells, a T-cell dependent process, is markedly decreased. We analyzed the defective capacity to produce Ig in vitro in 11 patients with SLE and 11 with MCTD. PWM-activated PB T-cells, both from SLE- and MCTD-patients, did not differ from control T-cells in their capacity to produce B-cell growth factors (BCGF) and B-cell differentiation factors (BCDF). However, B-cell proliferative responsiveness to control T-cell factors was decreased compared to control B-cells (p less than 0.01). In contrast to PB B-cells splenic B-cells from a patient with MCTD who underwent splenectomy were highly responsive to T-cell factors in a dose dependent way. It is concluded that the defective PWM-induced Ig production of PB lymphocytes in SLE/MCTD is due to decreased responsiveness of PB B cells to T-cell factors. However, analysis of splenic lymphocytes may be more representative for evaluation of the immunoregulatory disturbances in these disorders.