Immunological Tolerance to the Thymus‐Independent Antigen Dextran can be Abrogated by Thymus‐Dependent Dextran Conjugates: Evidence against Clonal Deletion as the Mechanism of Tolerance Induction

Abstract

Tolerance to the .alpha.1-6 epitope of native dextran B512 was very stable and could not be broken by the injection of dextran conjugated to several substances, such as protein A, keyhole limpet hemocyanin, edistin, concanavalin A or Staphylococcus strain Cowan. When tolerant mice were injected with dextranase, all the above conjugates induced a strong anti-.alpha.1-6 immune response. Native dextran itself never induced a response in tolerant, dextranase-treated mice. Apparently tolerance only affects the specific B[bone marrow derived]-cell subpopulation that can respond to the polyclonal B-cell-activating (PBA) property of dextran; other specific B cells having PBA receptors for, e.g., signals delivered by collaborating T [thymus derived] cells remain in a resting state. These B cells can respond in a specific immune response against the tolerogen after removal of the antigen, which blocks the Ig [immunoglobulin] receptors and therefore prevents them from passively focusing the antigen. Thus, immunological tolerance is not caused by clonal elimination of the antigen-specific clone, but only affects a small subfraction of cells with Ig receptors against the tolerogen.