Cellular events in protein tolerant inbred rats. II. Antibody avidity maturation during induction and loss of tolerance

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Abstract
Complete and partial states of tolerance were induced in (AS2 x AS)F1 hybrid rats after single or repeated injections of high, medium and low doses of fluid HSA (100 mg to 10 μg). Changes in antibody avidity, following challenge with HSA plus adjuvant, were used to detect those affinity subclasses of HSA‐specific cells which were not eliminated by tolerogenic antigen.Rats undergoing prolonged low dose treatments of fluid HSA induced an appreciable quantity of high avidity antibody before challenge. The avidity decreased significantly following challenge, indicating a progressive loss of high affinity cells, but only after the synthesis of antibody. Rats made partially tolerant against large and medium doses of fluid HSA when challenged, synthesized antibody which failed to mature to a high level, indicating again that high affinity cells were among the first to be deleted. The higher affinity cells in primed rats (including partially unresponsive rats) were the first to disappear during the memory response which was also triggered by fluid HSA. It is proposed that protein antigens induce a state of tolerance by eliminating B cells, but only after driving them through a stage of antibody synthesis.Avidity of antibody was measured following restoration of HSA responsiveness. Antibody failed to mature to a high level in previously tolerant rats that were allowed to recover naturally (stem cell replacement) or were given normal thoracic duct lymphocytes after the tolerance inducing treatment.