Mechanism of termination of immunological tolerance.

Mice were rendered tolerant to bovine serum albumin (BSA) by means of cyclophosphamide. The effect of immunization with sulphanilated BSA with different degrees of hapten conjugation on this tolerant state was examined. It was shown that the tolerant state was readily terminated with sulphanilated BSA with a low degree of chemical modification. Specificities of antibodies produced in response to sulphanilated BSA were tested by absorption and PHA inhibition test, demonstrating that there were antibodies directed to new antigenic determinant(s) on sulphanilate BSA as well as those reacting with unmodified BSA. To explore the cellular mechanism of termination, lethally irradiated syngeneic mice were reconstituted with thymus-derived cells (T cells) together with bone marrow-derived cells (B cells) from either normal mice or mice rendered tolerant to BSA, and were immunized with BSA or sulphanilate BSA. Tolerance termination was clearly observed in the recipient mice reconstituted with tolerant T cells plus normal B cells. From these experimental data, it was proposed that the termination was effected by means of the co-operation of the T-cell population tolerant to BSA but capable of responding to new antigenic determinant(s) on sulphanilated BSA, with non-tolerant B cells responsive to BSA.