In vivo and in vitro study of the primary and secondary antibody response to a bacterial antigen in aged mice

One of the most important manifestations of aging in both humans and laboratory animals is a gradual decline in immune effectiveness. However, it is not clear as to how general is this decline. We here report that aged BALB/c mice showed no decline in the magnitude of the in vivo primary antibody response to phosphorylcholine (PC), an immunodominant epitope of the Streptococcus pneumoniae R36a (Pn). Often it appeared that aged mice responded better than young syngeneic mice. In contrast, the secondary antibody response had a different profile, with aged mice showing a marked decrease in PC-specific antibody. Further in vitro studies were conducted in order to determine the cause of the decline of the secondary antibody response in aging. We noted that B cells from young and aged donors, either primed or twice immunized with the antigen, when cultured without T cells and in the presence of antigen did not display any significant difference in their antibody response to PC. However, L3T4 cells from aged BALB/c mice, previously immunized twice with Pn, failed to augment the in vitro B cell response as compared to L3T4 cells from young mice. Moreover, we found that Lyt 2 cells from young and aged mice had no regulatory effects on the anti-PC response in vitro. Further in vivo experiments demonstrated that alteration of the idiotypic network may not be related to a decline in the secondary antibody response since two injections of the antigen are unable to elicit an anti-idiotypic antibody response in either young or aged mice. These data demonstrate that the decline of the anti-PC response after a secondary challenge with Pn is linked to defects in the T cell compartment