Differences in the mechanism of tolerance to dinitrophenylated bovine gamma globulin when induced in normal adult mice or in reconstituted irradiated mice: dependence of the mechanism of tolerance on the structural organization of the lymphoid system.

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Abstract
Tolerance can be induced in adult mice by a single i.v. injection of 0.5 mg dinitrophenylated bovine .gamma.-globulin. The cellular mechanism of the unresponsive state is different depending upon whether the tolerance is induced in normal intact adult mice or in reconstituted, irradiated mice. The tolerant state induced in intact mice is characterized by a high avidity of the residual antibody-forming cells in partially tolerant animals and a prompt reversibility on cell transfer. This unresponsive state is apparently mediated by the production of small amounts of high affinity antibody in response to the tolerance-inducing injection of antigen. The unresponsiveness induced in reconstituted, irradiated mice by the same procedure was charazterized by a low avidity of the residual antibody-forming cells in partially tolerant animals and stability on transfer of spleen cells from unresponsive into irradiated recipients. No suppressor cell activity was detected. Mixed cell transfer studies showed that this unresponsive state represented a B[bone marrow-derived]-lymphocyte clonal deletion. The presence or absence of T [thymus-derived] lymphocytes in the population of cells used for reconstituting the irradiated recipients did not effect the ease of tolerance induction or the cellular mechanism of the tolerant state which was produced. If irradiated mice reconstituted with B and T lymphocytes were rested for 2 wk before tolerance induction then a reversible high affinity -type tolerance is obtained such as is typical of normal intact animals. Restoration of a normal response to the tolerance-inducing injection of antigen is dependent upon the presence of thymus cells in the population of cells used for reconstitution. The structural integrity of the lymphoid tissue is critical in determining whether B cells will be rendered tolerant after exposure to antigen in vivo.