Irradiation-mediated rescue of T cell-specific V(D)J recombination and thymocyte differentiation in severe combined immunodeficient mice by bone marrow cells

In SCID (severe combined immunodeficient) mice, proper assembly of immunogl obulin and T cell receptor (TCR) genes is blocked by defective V(D)J recomb ination so that B and T lymphocyte differentiation is arrested at an early precursor stage. Treating the mice with gamma irradiation rescues V(D)J rea rrangement at multiple TCR loci, promotes limited thymocyte differentiation , and induces thymic lymphomas. These effects are not observed in the B cel l lineage. Current models postulate that irradiation affects intrathymic T cell precursors. Surprisingly, we found that transfer of irradiated SCID bo ne marrow cells to unirradiated host animals rescues both TCR rearrangement s and thymocyte differentiation. These data indicate that irradiation affec ts precursor cells at an earlier stage of differentiation than was previous ly thought and suggest new models for the mechanism of irradiation rescue.