Suppression of Autoimmunity through Manipulation of Immune Network with Normal Immunoglobulin G

Expression of autoreactivity is efficiently regulated under physiological conditions to maintain the homeostasis of the immune system, thus preventing the emergence of autoaggressive T and B cell clones. Selection of preimmune repertoires and control of autoreactivity in healthy individuals involve variable (V) region interactions between antibodies and lymphocytes within a functional network (Sundblad 1991). The emergence of pathological autoimmunity could reflect a failure in the function of immune network. Following this view, therapeutic intervention in autoimmunity should primarily be aimed at stimulating the molecular and cellular mechanisms involved in physiological regulation of autoreactivity. We propose that these concepts provide a basis for understanding the therapeutic effects of the infusion of pooled normal polyspecific IgG (intravenous immunoglobulins: IVIg) in patients with autoimmune diseases. In this review, we discuss the evidence supporting the hypothesis that the immunoregulatory effect of IVIg in autoimmune disease is dependent on the selection of recipient’s immune repertoires by V region reactivities of infused IgG.