The Immunoglobulin Sequence

Summary The local administration of bovine γ-globulin (BγG) to rabbits evoked a characteristic sequence of immunoglobulin synthesis: γM antibodies followed by γG antibodies. This progression of the immune response was disrupted by 6-mercaptopurine (6-MP), and rabbits so treated produced low titers of γG antibodies but normal amounts of γM antibodies. The period of γM synthesis was abnormally prolonged in 6-MP-treated rabbits. Passively infused, specific, reactive γG anti-BγG antibodies arrested the formation of γM anti-BγG antibodies in normal and 6-MP-treated rabbits. A second dose of antigen given to 6-MP-treated rabbits resulted in the rapid appearance of γG antibodies and the cessation of γM antibody synthesis. Splenectomized rabbits given a local injection of BγG had enhanced levels of γG antibodies. Splenectomy abolished the disruptive effects of 6-MP on the immunoglobulin sequence. The results of these experiments indicate: a) the process of γG antibody synthesis is more susceptible to the anti-metabolic action of 6-MP than that of γM formation; b) γG antibody exerts a negative feedback effect on the formation of γM antibody; c) antigen may play a direct and intimate role in the actual synthesis of γG antibodies; and d) under certain conditions, the spleen may inhibit the production of γG antibodies.