Cellular mechanisms of escape from immunological tolerance.

Immunological tolerance to human serum albumin (HSA) was induced in chickens by large doses of antigen injected post-hatching. Bursectomy or thymectomy performed at the age of 2 weeks did not affect the responsiveness of normal birds but interfered specifically with the recovery of immunity to HSA in tolerant chickens. The kinetics of recovery and type of antibody produced depended on the dose of antigen used for challenge: early and full recovery of IgG antibody followed challenge with 100 mg HSA; delayed and partial recovery of IgM with no IgG recovery followed challenge with 1 mg HSA. Bursectomy interfered with loss of tolerance at both dosages, whereas thymectomy was effective only following challenge with 10–100 mg HSA. This is interpreted as evidence for cell-replacement of B-cells in the peripheral tissues during escape from tolerance. The data are discussed in terms of triggering and inactivation of B-lymphocytes in various anatomical sites. It is postulated that cell replacement is operated by both virgin and antigen-experienced precursor cells.