The role of the thymus in a genetically controlled defect of the immune response at the carrier level.

The genetic control of the immune response may be either specific for antigenic carrier or for determinant. We describe here results which show that a carrier-dependent strain defect in immune response is reflected in thymocytes. These results are in agreement with our hypothesis that the genetic defect in the immune response is reflected in thymocytes when the poor response is at the carrier level, whereas it is expressed in the bone marrow population when the low responsiveness is strictly at the determinant level. SWR mice are low responders to multichain polyproline. Furthermore, this mouse strain does not produce antibodies to determinants such as peptides of phenylalanine and glutamic acid (Phe,Glu) or to the loop peptide of lysozyme when attached to polyproline, although they respond well to the same antigenic determinants when conjugated to multichain poly(DL-alanine). Transfer experiments in which irradiated SWR recipients were injected with excess of DBA/1 thymocytes (which do not exhibit a defect in response to polyproline) mixed with graded numbers of SWR marrow cells, prior to immunization with poly(Tyr,Glu)-poly(Pro)--poly(Lys), have indicated that the poor response potential of SWR mice to polyproline is not reflected in their bone marrow cells. Allogeneic transfers in which mixtures of thymocytes and marrow cells from high and low responders were injected into irradiated mice, followed by immunization with poly(Tyr,Glu)-poly(Pro)--poly(Lys) or poly(Phe,Glu)-poly(Pro)--poly(Lys) have demonstrated a clear defect in the thymus derived population of SWR mice when the response potential to polyproline and to determinants attached to it was tested.