A hapten, 4-hydroxy-3-iodo-5-nitrophenylacetic acid (NIP) when coupled to isologous mouse gamma globulin (MγG) elicits a hapten-specific immune response in mice if administered in Freund's complete adjuvant. This response is measurable by the capacity of the sera to bind N125IP, by detection of NIP-specific plaque-forming cells (B cells), and by in vitro secondary type antigen-driven DNA synthesis (T cells and probably B cells). The in vitro response requires both the hapten and carrier since neither by itself is capable of stimulating the spleen cells. This same antigen gives rise to hapten-specific tolerance when given in the soluble form. Mice pretreated with soluble NIP-MγG and challenged with NIP coupled to a heterologous carrier give a normal antibody response to the carrier but have barely detectable levels of antibody to NIP. Spleen cells from mice made tolerant to NIP-MγG do not respond in vitro with increased DNA synthesis. This implies that thymus-derived cells as well as bone marrow-derived cells are involved in hapten-specific tolerance.

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