Repertoire diversity of antibody response to bacterial antigens in aged mice. III. Phosphorylcholine antibody from young and aged mice differ in structure and protective activity against infection with Streptococcus pneumoniae.

Abstract

Aging in mice is accompanied by qualitative changes in the antibody repertoire to phosphorylcholine (PC), a natural epitope of certain pneumococci. The PC-specific mAb from young/adult (2-4 mo) BALB/c mice are uniformly encoded by the canonical IgV genes of T15 family, whereas the antibody from aged mice (> or = 20 mo) are molecularly heterogeneous, being encoded by various VH and VL genes of non-T15 families. Interestingly the young/adult and aged BALB/c mice produce comparable amounts of antibodies to PC regardless of the molecular shift in the antibody repertoire. This finding prompted our study on the relative ability of PC antibodies from young and aged donors to protect mice against virulent infection with type 3 pneumococci. Passive administration (i.p.) of pooled, PC-specific mAb generated from young donors (all from the T15 Ig gene family) protected the recipients against subsequent i.p. challenge with a lethal dose of Streptococcus pneumoniae strain WU2, in a dose-dependent manner. In contrast, a mixture of PC mAb from aged donors (all from non-T15 families) failed to protect the mice against the infection, even at the highest amount of administered (100 micrograms of mAb/recipient). Average affinity of the aged mAb for the free hapten (PC-chloride) as well as their binding to the bacteria was lower than that of the young mAb. Similarly, affinity-purified serum PC antibody from S. pneumoniae vaccine-immunized young mice afforded a measurable degree of passive protection against the pneumococcal infection whereas a similar dose of serum PC antibody from aged mice did not. Further experiments showed that PC mAb from young donors were equally protective in either young or aged recipients challenged with the bacteria. These results demonstrate that the aged immune system may, in some instances, produce high levels of antibody that are structurally different and less protective against microbial infection.