title: 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.
abstract: The effects of age, genetic background, and neonatal thymectomy on the levels and the heterogeneity of the specific antibody response were investigated in an experimental mouse model. Both intact and neonatally thymectomized (NTx) C57BL/KaLwRij (C57BL) and CBA/BrARij (CBA) mice were immunized at the age of 3 ("young") or 22 months ("old"). Highly sensitive antigen-specific immunoblotting techniques (ABL), in combination with agar-electrophoresis and isoelectric focusing (IEF), were used to investigate total specific antibody levels, the number of responding 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 progressively increased in all experimental groups with the exception of old C57BL mice. All mice responded with a specific polyclonal heterogeneous response. In addition, some mice showed a clonal dominance of antibody-producing cells, as is reflected in the appearance of distinct homogeneous antibody components (H-Ab) in the sera. This clonal dominance was scarce in CBA mice but frequent in C57BL mice. Age at time of immunization and NTx had little if any additive effect on the incidence of H-Ab in either mouse strain. All dominant clones showed different electrophoretic mobility, indicating the proliferation of various clonotypes and not a strain-specific dominance of one clone. In old C57BL mice the specific antibody response was more restricted in heterogeneity, as is illustrated by more visible spectrotype bands in IEF and subsequent ABL. Hence, in old C57BL mice smaller amounts of specific antibodies were produced by fewer clones. Still, the incidence of H-Ab in this group was the same as that in the group of young C57BL mice. This indicates that at old age the responding B cell clones are more prone to becoming clonally dominant in C57BL mice. This tendency correlates with the high incidence of spontaneously developing monoclonal gammopathies in aging C57BL mice.
authors.affiliation: Department of Immunological and Infectious Diseases, TNO Prevention and Health, Leiden, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: van Arkel
authors.forename: F J
authors.initials: FJ
authors.lastname: Nooij
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Sluijs-Gelling
authors.forename: J
authors.initials: J
authors.lastname: Radl
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000917:Antibody Formation / Q000502:physiology*; D000918:Antibody Specificity / Q000235:genetics; D004140:Dinitrophenols / Q000276:immunology*; D004587:Electrophoresis, Agar Gel; D018740:Genetic Heterogeneity; D007114:Immunization; D015151:Immunoblotting; D007525:Isoelectric Focusing; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010265:Paraproteinemias / Q000209:etiology*; D012709:Serum Albumin / Q000276:immunology*
chemical_list: D004140:Dinitrophenols; D012709:Serum Albumin; C058064:dinitrophenyl-human serum albumin conjugate