Repertoire diversity of antibody response to bacterial antigens in aged mice. II. Phosphorylcholine-antibody in young and aged mice differ in both VH/VL gene repertoire and in specificity

Abstract

Aging of mice is accompanied by both quantitative and qualitative changes in antibody responses to phosphorylcholine (PC), an immunodominant epitope of Streptococcus pneumoniae R36a strain (Pn). In order to study these changes at the molecular level, we generated PC-specific hybridomas from young (3 to 4 mo) and aged (20 to 24 mo) mice of different strains after primary immunization with S. pneumoniae R36a strain. These mAb were tested for Ig VH and VL gene family utilization, idiotopic repertoire, and cross-reactivity with unrelated Ag. Hybridomas from young mice (BALB/c, C57BL/6, and D1.LP) uniformly expressed the VH-S107 and V kappa-22 genes as well as most idiotopes of the T15 family, which were identified with different anti-T15 mAb. In contrast, the PC-reactive mAb from aged mice were quite heterogeneous: only 2 out of 13 utilized VHS107, 1 of 13 used VH7183, and 3 of 13 used VHJ558 gene family. Moreover, none of these mAb used L chain encoded by V kappa 22(0/13), but surprisingly they frequently expressed some of the T15 idiotope. In addition, the PC-binding mAb from aged mice showed broad cross-reactivity with various mouse and foreign proteins, whereas the mAb from young mice did not. These results demonstrate the genetic shift in antibody response of aging mice to PC, which is accompanied by a change in the antibody specificity. Interestingly, the qualitative repertoire change appears to be unrelated to the magnitude of antibody response, for the aged BALB/c mice maintain a very high reactivity to PC.