FREQUENCY OF CLONAL DOMINANCE IN THE SPECIFIC ANTIBODY-RESPONSE TO DNP-HSA IN CBA AND C57BL MICE REFLECTS THEIR SUSCEPTIBILITY TO AGE-ASSOCIATED DEVELOPMENT OF MONOCLONAL GAMMOPATHIES

The effects of age, genetic background, and neonatal thymectomy on the levels and the heterogeneity of the specific antibody response were i nvestigated in an experimental mouse model. Both intact and neonatally thymectomized (NTx) C57BL/KaLwRij (C57BL) and CBA/BrARij (CBA) mice w ere immunized at the age of 3 (''young'') or 22 months (''old''). High ly sensitive antigen-specific immunoblotting techniques (ABL), in comb ination with agar-electrophoresis and isoelectric focusing (IEF), were used to investigate total specific antibody levels, the number of res ponding antigen-specific clonotypes, and the dominance of responding B cell clones in the antibody response against dinitrophenylated human serum albumin. After immunization, the specific antibody levels progre ssively increased in all experimental groups with the exception of old C57BL mice. All mice responded with a specific polyclonal heterogeneo us response. In addition, some mice showed a clonal dominance of antib ody-producing cells, as is reflected in the appearance of distinct hom ogeneous antibody components (H-Ab) in the sera. This clonal dominance was scarce in CBA mice but frequent in C57BL mice. Age at time of imm unization and NTx had little if any additive effect on the incidence o f H-Ab in either mouse strain. All dominant clones showed different el ectrophoretic mobility, indicating the proliferation of various clonot ypes and not a strain-specific dominance of one clone. In old C57BL mi ce the specific antibody response was more restricted in heterogeneity , as is illustrated by more visible spectrotype bands in IEF and subse quent ABL. Hence, in old C57BL mice smaller amounts of specific antibo dies were produced by fewer clones. Still, the incidence of H-Ab in th is group was the same as that in the group of young C57BL mice. This i ndicates that at old age the responding B cell clones are more prone t o becoming clonally dominant in C57BL mice. This tendency correlates w ith the high incidence of spontaneously developing monoclonal gammopat hies in aging C57BL mice. (C) 1997 Academic Press.