Antibody protection in aging: influence of idiotypic repertoire and antibody binding activity to a bacterial antigen.
Previous studies demonstrated that the anti-phosphorylcholine (PC) antibodies produced by aged BALB/c (18-22 months old) mice are structurally different and less protective against infection with Streptococcus pneumoniae than those produced by young (3-4 months old) syngeneic mice. However, PC antibody from aged animals had a different idiotypic repertoire and, at the same time, showed a diminished antibody binding activity to pneumococci compared to "young" antibody. To determine the cause of the reduced protective activity of the "aged" antibody, experiments of passive protection were performed using anti-PC monoclonal antibody (mAb) from either young and aged BALB/c or young syngeneic mice that were neonatally injected with an equimolar mixture of two monoclonal antibodies specific for two distinct idiotopes of the T15 idiotype (Id) family. At young/adult age, the mice neonatally injected with anti-Id antibody were still able to respond to PC, but the idiotypic repertoire was characterized by the absence of the dominant T15 idiotype. The two groups of mAb generated had a similar affinity to PC and binding activity to pneumococci but were totally diverse in regard to both their idiotypic repertoire and VH/VL gene utilization. Experiments of passive protection allowed us to determine the influence of the idiotypic repertoire and antibody binding activity to pneumococci on the reduced antibody protective efficiency in aging. Young recipients (BALB/c) were injected ip with a dose of anti-PC mAb from young, either T15Id+ or T15Id-, and aged donors (20 micrograms/recipient) and 2 hr later the groups of mice were challenged with 10(3) CFU of S. pneumoniae WU-2. Both groups of "young" antibody afforded a similar degree of protection, regardless of the idiotypic repertoire, always higher than that of PC antibody from aged mice. These experiments suggested that the decline of binding activity, and not the switch in the idiotypic repertoire, may be responsible for the reduced anti-pneumococcal activity of the anti-PC antibody on aging.
Abteilung Immunchemie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
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Nicoletti
D000375:Aging / Q000276:immunology*; D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions; D000942:Antigens, Bacterial / Q000276:immunology*; D001666:Binding Sites, Antibody; D005260:Female; D005803:Genes, Immunoglobulin; D006825:Hybridomas; D007116:Immunization, Passive; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010767:Phosphorylcholine / Q000276:immunology*; D011008:Pneumococcal Infections / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013997:Time Factors
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D007130:Immunoglobulin Idiotypes; D010767:Phosphorylcholine