CONSTITUTIVE EXPRESSION OF IL-6 RECEPTORS AND THEIR ROLE IN THE EXCESSIVE B-CELL FUNCTION IN PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS

Excessive B cell function including autoantibody production is a commo n feature of SLE and considered to be intimately associated with spont aneous lymphokine secretion by themselves. To clarify roles of IL-6/IL -6 receptor autocrine activation pathway in autoantibody production ob served in patients with SLE, we studied expression and function of IL- 6 receptors in comparison with those of IL-2 receptors, Tac on SLE B c ells. IL-6 receptors and IL-2 receptors have been detected on B cells in the blood without any in vitro stimuli in most patients with SLE. T he introduction of anti-IL-6 receptor antibody, which inhibits binding to the receptors of IL-6, and anti-IL-2 receptor antibody, anti-Tac t o the cultures of SLE B cells resulted in potent inhibition of spontan eous production of polyclonal Ig and anti-DNA autoantibodies. In addit ion, fresh SLE B cells secreted high levels of IL-6 without any in vit ro stimuli. These results indicate that constitutive expression of IL- 6 receptors on B cells in conjunction with spontaneous IL-6 production by B cells induces autocrine B cell activation, which may lead to B c ell hyperactivity and autoantibody secretion in SLE patients. Dysregul ation of B cell activity observed in patients with SLE could thus be, at least in part, independent of T cell help.