Development of aging-associated monoclonal gammapathies with antibody activity to the antigen used for immunization of young mice.

The influence of immunization with dinitrophenylated human serum albumin (DNP-HSA) at a young age on the development of age-related monoclonal gammapathies (MG) was investigated in a longitudinal study in intact and neonatally thymectomized (NTx) C57BL/KaLwRij and CBA/BrARij mice. Three-month-old mice were immunized four times in monthly intervals with DNP-HSA. Control mice received saline and adjuvant only. Mice immunized with DNP-HSA responded with heterogeneous antibodies, occasionally with some clonal dominance. The antibody levels further declined and were hardly detectable when the mice were 21 months old. Eighteen of 87 experimental mice developed homogeneous antibody components (H-Ab) to DNP-HSA with aging. Their frequencies per individual groups were 5, 22, 24, and 29% for intact CBA, NTx-CBA, NTx-C57BL, and intact C57BL mice, respectively. Some H-Ab had the same mobility and similar spectrotypes as dominant clonal products at the peak of the response. However, the majority of H-Ab appearing at old age were "new" H-Ab. While most of H-Ab in the CBA mice were transient and of a low concentration, the majority of H-Ab in the C57BL mice had all characteristics of a benign monoclonal gammapathy. The results indicate that memory cells of the B cell clones involved in the original specific response may in a susceptible strain become targets for events leading to the development of benign monoclonal gammapathy.