ANTIBODY PROTECTION IN AGING - INFLUENCE OF IDIOTYPIC REPERTOIRE AND ANTIBODY-BINDING ACTIVITY TO A BACTERIAL-ANTIGEN

Previous studies demonstrated that the anti-phosphorylcholine (PC) ant ibodies produced by aged BALB/c (18-22 months old) mice are structural ly different and less protective against infection with Streptococcus pneumoniae than those produced by young (3-4 months old) syngeneic mic e. However, PC antibody from aged animals had a different idiotypic re pertoire and, at the same time, showed a diminished antibody binding a ctivity to pneumococci compared to ''young'' antibody. To determine th e cause of the reduced protective activity of the ''aged'' antibody, e xperiments of passive protection were performed using anti-PC monoclon al antibody (mAb) from either young and aged BALB/c or young syngeneic mice that were neonatally injected with an equimolar mixture of two m onoclonal antibodies specific for two distinct idiotopes of the T15 id iotype (Id) family. At young/adult age, the mice neonatally injected w ith anti-Id antibody were still able to respond to PC, but the idiotyp ic repertoire was characterized by the absence of the dominant T15 idi otype. The two groups of mAb generated had a similar affinity to PC an d binding activity to pneumococci but were totally diverse in regard t o both their idiotypic repertoire and V-H/V-L gene utilization. Experi ments of passive protection allowed us to determine the influence of t he idiotypic repertoire and antibody binding activity to pneumococci o n the reduced antibody protective efficiency in aging. Young recipient s (BALB/c) were injected ip with a dose of anti-PC mAb from young, eit her T15Id(+) or T15Id(-), and aged donors (20 mu g/recipient) and 2 hr later the groups of mice were challenged with 10(3) CFU of S. pneumon iae WU-2. Both groups of ''young'' antibody afforded a similar degree of protection, regardless of the idiotypic repertoire, always higher t han that of PC antibody from aged mice. These experiments suggested th at the decline of binding activity, and not the switch in the idiotypi c repertoire, may be responsible for the reduced anti-pneumococcal act ivity of the anti-PC antibody on aging. (C) 1995 Academic Press,Inc.