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 immunoglobulin and T cell receptor (TCR) genes is blocked by defective V(D)J recombination 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...

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Detalles Bibliográficos
Autores principales: Wang, Chiyu, Bogue, Molly A., Levitt, Jonathan M., Roth, David B.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Original Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195679/
https://www.ncbi.nlm.nih.gov/pubmed/10544197
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author Wang, Chiyu
Bogue, Molly A.
Levitt, Jonathan M.
Roth, David B.
author_facet Wang, Chiyu
Bogue, Molly A.
Levitt, Jonathan M.
Roth, David B.
author_sort Wang, Chiyu
collection PubMed
description In SCID (severe combined immunodeficient) mice, proper assembly of immunoglobulin and T cell receptor (TCR) genes is blocked by defective V(D)J recombination so that B and T lymphocyte differentiation is arrested at an early precursor stage. Treating the mice with gamma irradiation rescues V(D)J rearrangement at multiple TCR loci, promotes limited thymocyte differentiation, and induces thymic lymphomas. These effects are not observed in the B cell lineage. Current models postulate that irradiation affects intrathymic T cell precursors. Surprisingly, we found that transfer of irradiated SCID bone marrow cells to unirradiated host animals rescues both TCR rearrangements and thymocyte differentiation. These data indicate that irradiation affects precursor cells at an earlier stage of differentiation than was previously thought and suggest new models for the mechanism of irradiation rescue.
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spelling pubmed-21956792008-04-16 Irradiation-Mediated Rescue of T Cell–Specific V(D)j Recombination and Thymocyte Differentiation in Severe Combined Immunodeficient Mice by Bone Marrow Cells Wang, Chiyu Bogue, Molly A. Levitt, Jonathan M. Roth, David B. J Exp Med Original Article In SCID (severe combined immunodeficient) mice, proper assembly of immunoglobulin and T cell receptor (TCR) genes is blocked by defective V(D)J recombination so that B and T lymphocyte differentiation is arrested at an early precursor stage. Treating the mice with gamma irradiation rescues V(D)J rearrangement at multiple TCR loci, promotes limited thymocyte differentiation, and induces thymic lymphomas. These effects are not observed in the B cell lineage. Current models postulate that irradiation affects intrathymic T cell precursors. Surprisingly, we found that transfer of irradiated SCID bone marrow cells to unirradiated host animals rescues both TCR rearrangements and thymocyte differentiation. These data indicate that irradiation affects precursor cells at an earlier stage of differentiation than was previously thought and suggest new models for the mechanism of irradiation rescue. The Rockefeller University Press 1999-11-01 /pmc/articles/PMC2195679/ /pubmed/10544197 Text en © 1999 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Original Article
Wang, Chiyu
Bogue, Molly A.
Levitt, Jonathan M.
Roth, David B.
Irradiation-Mediated Rescue of T Cell–Specific V(D)j Recombination and Thymocyte Differentiation in Severe Combined Immunodeficient Mice by Bone Marrow Cells
title Irradiation-Mediated Rescue of T Cell–Specific V(D)j Recombination and Thymocyte Differentiation in Severe Combined Immunodeficient Mice by Bone Marrow Cells
title_full Irradiation-Mediated Rescue of T Cell–Specific V(D)j Recombination and Thymocyte Differentiation in Severe Combined Immunodeficient Mice by Bone Marrow Cells
title_fullStr Irradiation-Mediated Rescue of T Cell–Specific V(D)j Recombination and Thymocyte Differentiation in Severe Combined Immunodeficient Mice by Bone Marrow Cells
title_full_unstemmed Irradiation-Mediated Rescue of T Cell–Specific V(D)j Recombination and Thymocyte Differentiation in Severe Combined Immunodeficient Mice by Bone Marrow Cells
title_short Irradiation-Mediated Rescue of T Cell–Specific V(D)j Recombination and Thymocyte Differentiation in Severe Combined Immunodeficient Mice by Bone Marrow Cells
title_sort irradiation-mediated rescue of t cell–specific v(d)j recombination and thymocyte differentiation in severe combined immunodeficient mice by bone marrow cells
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195679/
https://www.ncbi.nlm.nih.gov/pubmed/10544197
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