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Enhanced B Cell Expansion, Survival, and Humoral Responses by Targeting Death Receptor 6
Targeted disruption of death receptor (DR)6 results in enhanced CD4(+) T cell expansion and T helper cell type 2 differentiation after stimulation. Similar to T cells, DR6 is expressed on resting B cells but is down-regulated upon activation. We examined DR6(−/−) B cell responses both in vitro and i...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193799/ https://www.ncbi.nlm.nih.gov/pubmed/12515813 http://dx.doi.org/10.1084/jem.20020617 |
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author | Schmidt, Clint S. Liu, Jinqi Zhang, Tonghai Song, Ho Yeong Sandusky, George Mintze, Karen Benschop, Robert J. Glasebrook, Andrew Yang, Derek D. Na, Songqing |
author_facet | Schmidt, Clint S. Liu, Jinqi Zhang, Tonghai Song, Ho Yeong Sandusky, George Mintze, Karen Benschop, Robert J. Glasebrook, Andrew Yang, Derek D. Na, Songqing |
author_sort | Schmidt, Clint S. |
collection | PubMed |
description | Targeted disruption of death receptor (DR)6 results in enhanced CD4(+) T cell expansion and T helper cell type 2 differentiation after stimulation. Similar to T cells, DR6 is expressed on resting B cells but is down-regulated upon activation. We examined DR6(−/−) B cell responses both in vitro and in vivo. In vitro, DR6(−/−) B cells undergo increased proliferation in response to anti–immunoglobulin M, anti-CD40, and lipopolysaccharide. This hyperproliferative response was due, at least in part, to both increased cell division and reduced cell apoptosis when compared with wild-type B cells. Consistent with these observations, increased nuclear levels and activity of nuclear factor κB transcription factor, c-Rel, and elevated Bcl-x(l) expression were observed in DR6(−/−) B cells upon stimulation. In addition, DR6(−/−) B cells exhibited higher surface levels of CD86 upon activation and were more effective as antigen-presenting cells in an allogeneic T cell proliferation response. DR6(−/−) mice exhibited enhanced germinal center formation and increased titers of immunoglobulins to T-dependent as well as T-independent type I and II antigens. This is the first demonstration of a regulatory role of DR6 in the activation and function of B cells. |
format | Text |
id | pubmed-2193799 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21937992008-04-11 Enhanced B Cell Expansion, Survival, and Humoral Responses by Targeting Death Receptor 6 Schmidt, Clint S. Liu, Jinqi Zhang, Tonghai Song, Ho Yeong Sandusky, George Mintze, Karen Benschop, Robert J. Glasebrook, Andrew Yang, Derek D. Na, Songqing J Exp Med Article Targeted disruption of death receptor (DR)6 results in enhanced CD4(+) T cell expansion and T helper cell type 2 differentiation after stimulation. Similar to T cells, DR6 is expressed on resting B cells but is down-regulated upon activation. We examined DR6(−/−) B cell responses both in vitro and in vivo. In vitro, DR6(−/−) B cells undergo increased proliferation in response to anti–immunoglobulin M, anti-CD40, and lipopolysaccharide. This hyperproliferative response was due, at least in part, to both increased cell division and reduced cell apoptosis when compared with wild-type B cells. Consistent with these observations, increased nuclear levels and activity of nuclear factor κB transcription factor, c-Rel, and elevated Bcl-x(l) expression were observed in DR6(−/−) B cells upon stimulation. In addition, DR6(−/−) B cells exhibited higher surface levels of CD86 upon activation and were more effective as antigen-presenting cells in an allogeneic T cell proliferation response. DR6(−/−) mice exhibited enhanced germinal center formation and increased titers of immunoglobulins to T-dependent as well as T-independent type I and II antigens. This is the first demonstration of a regulatory role of DR6 in the activation and function of B cells. The Rockefeller University Press 2003-01-06 /pmc/articles/PMC2193799/ /pubmed/12515813 http://dx.doi.org/10.1084/jem.20020617 Text en Copyright © 2003, 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 | Article Schmidt, Clint S. Liu, Jinqi Zhang, Tonghai Song, Ho Yeong Sandusky, George Mintze, Karen Benschop, Robert J. Glasebrook, Andrew Yang, Derek D. Na, Songqing Enhanced B Cell Expansion, Survival, and Humoral Responses by Targeting Death Receptor 6 |
title | Enhanced B Cell Expansion, Survival, and Humoral Responses by Targeting Death Receptor 6 |
title_full | Enhanced B Cell Expansion, Survival, and Humoral Responses by Targeting Death Receptor 6 |
title_fullStr | Enhanced B Cell Expansion, Survival, and Humoral Responses by Targeting Death Receptor 6 |
title_full_unstemmed | Enhanced B Cell Expansion, Survival, and Humoral Responses by Targeting Death Receptor 6 |
title_short | Enhanced B Cell Expansion, Survival, and Humoral Responses by Targeting Death Receptor 6 |
title_sort | enhanced b cell expansion, survival, and humoral responses by targeting death receptor 6 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193799/ https://www.ncbi.nlm.nih.gov/pubmed/12515813 http://dx.doi.org/10.1084/jem.20020617 |
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