The data presented in this study document that the phospholipase A₂ (PLA₂)-specific IgE antibody response in high responder CBA/J mice is solely dependent on the antigen dose used for immunization. Repeated injections of minute doses (MD) of antigen (0.1 μg/mouse) induce a persisting high level of PLA₂-specific IgE antibody titer, whereas large doses (LD) (10 μg/mouse) induce a persisting low level of IgE. The IgG antibody titers are the same under both conditions. The low level IgE immune status induced by repeated LD is irreversible and cannot be boosted by MD. In contrast a single LD primes for a secondary IgE response which can be recalled by MD. A high level of PLA₂-specific IgE antibodies induced by MD can be downregulated by a single intervening LD of antigen. A low level IgE immune status can be transferred with spleen cells of mice immunized with LD into naive syngeneic recipients, which then fail to mount a high level IgE response upon injection of MD of antigen. The experiments reveal two countercurrent processes, induction of Bε-memory cells after a single LD and additional activation of a persisting IgE-specific cellular suppression mechanism after repeated LD of antigen. These properties make the system suitable for the analysis of cellular interactions and of potential desensitization protocols.