The effect of challenge by antigen on persistence of clones of antibody-producing cells and on the induction of new clones was investigated through quantitative measurements of idiotypic specificities.

In each of nine rabbits idiotypic specificities present in the earliest bleedings were completely replaced after a few months; subsequent changes occurred much more slowly. On a quantitative basis the population of molecules used as immunogen always reacted most effectively with the homologous anti-idiotypic antiserum.

Little effect of increased antigen dose on the rate of change of idiotype was observed. Even large amounts of antigen administered every 2 wk caused only gradual changes in idiotypic specificities. This was attributed either to more effective capture of antigen by memory cells, as compared to precursor cells, or to the induction of tolerance in those clones that were not expressed. In two of three rabbits on a monthly injection schedule, the idiotypic specificities identified underwent very slow changes over a period as long as 17 months. Changes occurred more rapidly when antigen was administered every 2 wk.

In each of four rabbits investigated, all idiotypic specificities identified before a 5 month rest period were still present afterwards, indicating the survival of essentially all clones of antibody-producing cells during that interval. Quantitative inhibition data indicated that some new clones of cells were initiated.

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