Diminished response to an inhibitory signal in lymphocytes from patients with systemic lupus erythematosus.

Systemic lupus erythematosus is an autoimmune disease characterized by B-cell hyperactivity, resulting in polyclonal hypergammaglobulinaemia. One mechanism potentially resulting in excessive immunoglobulin synthesis is a diminished response to inhibitory signals. To test this hypothesis, anti-IgG antisera was used to inhibit pokeweed mitogen activation of cultured lymphocytes from lupus patients and controls. Inhibition of IgG secretion by B cells from lupus patients required more than 75 times as much anti-IgG as normal controls (P less than 0.005), indicating that lupus lymphocytes are hyporesponsive to this inhibitory signal. Similar studies with DR3+ controls demonstrated that diminished responsiveness to anti-IgG inhibition may in part be associated with the HLA-DR3 allele. Defects in this inhibitory mechanism may play a role in the B-cell hyperactivity observed in lupus.