Effects of neonatal thymectomy and splenectomy on survival and regulation of autoantibody formation in NZB/NZW F1 mice

Abstract

NZW F1 (B/W) mice were subjected to sham surgery or neonatal thymectomy and/or splenectomy and studied for immunoglobulin class of antibodies to double-stranded DNA and polyadenylic acid (Poly A) at 4 to 13 months of age. These antibodies occur spontaneously during the course of autoimmune disease in B/W mice. Sera were fractionated by sucrose density gradient ultracentrifugation and assayed for antibodies by a filter radioimmunoassay method. IgM was recovered in the 19S region and IgG in the 7S region as demonstrated by immunodiffusion. In sham-operated controls, at all ages studied, anti-DNA antibodies were both IgM and IgG, with the former predominating in males, and the latter in females. In both sexes, anti-Poly A antibodies were primarily IgM in young mice. There was a sequential switch from IgM to either enhanced or new IgG production in the following sequence: female anti-DNA and anti-Poly A (6 months), male anti-DNA (9 months), and male anti-Poly A (11 months). Both thymectomy and splenectomy caused earlier death in male mice, whereas females lived significantly longer after thymectomy. Neonatal thymectomy in males caused a premature switch from IgM to IgG antibodies to DNA, but it had a transient effect in females. Thymectomy almost completely prevented the late switch to IgG antibodies to Poly A in both sexes. By contrast, splenectomy promoted the formation of IgG antibodies to Poly A in male mice. These results suggest that the newborn B/W thymus and spleen contain regulatory cells and/or factors exerting different controlling influences on spontaneous antibodies to DNA and Poly A. Male B/W mice appear to be under the regulatory influence of suppressor cells, whereas the predominant regulation in female B/W mice appears to be a helper effect.