Increase of cross(auto)-reactive antibodies after immunization in aged mice: a cellular and molecular study

Aging in both humans and laboratory animals is often accompanied by an increase in autoreactive antibodies. Here we report that immunization with a bacterial antigen determined a marked increase of cross-reactive antibodies in aged but not in young mice. This phenomenon was observed in the aged individuals of two different mouse strains (Balb/c and C57BL/6) after a single injection of lyophilized vaccine from Streptococcus pneumoniae R36a (Pn) that express the immunodominant epitope phosphorylcholine (PC). These data were then confirmed by the analysis of cross-reactivity of anti-PC monoclonal antibody (mAb) generated from Pn-immunized young and aged Balb/c and C57BL/6 mice. Most of the anti-PC mAb from aged mice showed a broad spectrum of cross-reactivity with a panel of self and non-self antigens, while none of the mAb from young mice did so. We also showed that a genetic shift, in the VH/VL gene repertoire of anti-PC antibody, appeared to take place in aged mice and that aged mAb displayed a decrease in antibody affinity for the free hapten PC as compared to the young ones. We interpret these data as showing that immunization at advanced age may be linked to the production of cross-reactive antibodies and that this event may be related to the increased incidence of autoantibody in the aged.