Suppression of Lymphoproliferation and Autoimmunity by Elimination of a Radiosensitive Bone Marrow Cell in Mice Bearing the lpr Gene

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Abstract
The autosomal recessive lpr (lymphoproliferative) gene has been bred into several normal strains of mice. Although the time of disease onset may vary, all of the lpr mice develop hypergammaglobulinemia, antibodies to nucleoproteins and massive lymphoproliferation. The abnormalities do not appear in their normal congeneic counterparts, which lack the lpr gene. The effects of sublethal whole-body X-irradiation (30 rad) on disease features and lymphocyte subpopulations was studied by using flow cytometry. H-2k strains, C3H and MRL/++ and their autoimmune lpr counterparts, were killed at 1, 2, 4, 8 and 24 wk after irradiation, which was given at 6-8 wk of age. In the lpr mice, lymphoproliferation, autoimmunity, mortality and number of Ia+ cells were greatly reduced in the irradiated mice compared with nonirradiated controls. Abnormal cytofluorometric patterns seen with lpr thymocytes were corrected by the low-dose irradiation treatment. Lethally irradiated lpr mice reconstituted with syngeneic bone marrow from low-dose irradiated mice exhibited retarded development of autoimmune disease. The lymphoid alterations induced by X-irradiation apparently reflect a recovery of immunologic control associated with suppression of autoimmune manifestations.