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TLR4 signaling augments B lymphocyte migration and overcomes the restriction that limits access to germinal center dark zones
B lymphocyte–intrinsic Toll-like receptor (TLR) signals amplify humoral immunity and can exacerbate autoimmune diseases. We identify a new mechanism by which TLR signals may contribute to autoimmunity and chronic inflammation. We show that TLR4 signaling enhances B lymphocyte trafficking into lymph...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806604/ https://www.ncbi.nlm.nih.gov/pubmed/19917774 http://dx.doi.org/10.1084/jem.20091982 |
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author | Hwang, Il-Young Park, Chung Harrison, Kathleen Kehrl, John H. |
author_facet | Hwang, Il-Young Park, Chung Harrison, Kathleen Kehrl, John H. |
author_sort | Hwang, Il-Young |
collection | PubMed |
description | B lymphocyte–intrinsic Toll-like receptor (TLR) signals amplify humoral immunity and can exacerbate autoimmune diseases. We identify a new mechanism by which TLR signals may contribute to autoimmunity and chronic inflammation. We show that TLR4 signaling enhances B lymphocyte trafficking into lymph nodes (LNs), induces B lymphocyte clustering and interactions within LN follicles, leads to sustained in vivo B cell proliferation, overcomes the restriction that limits the access of nonantigen-activated B cells to germinal center dark zones, and enhances the generation of memory and plasma cells. Intravital microscopy and in vivo tracking studies of B cells transferred to recipient mice revealed that TLR4-activated, but not nonstimulated, B cells accumulated within the dark zones of preexisting germinal centers even when transferred with antigen-specific B cells. The TLR4-activated cells persist much better than nonstimulated cells, expanding both within the memory and plasma cell compartments. TLR-mediated activation of B cells may help to feed and stabilize the spontaneous and ectopic germinal centers that are so commonly found in autoimmune individuals and that accompany chronic inflammation. |
format | Text |
id | pubmed-2806604 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28066042010-05-23 TLR4 signaling augments B lymphocyte migration and overcomes the restriction that limits access to germinal center dark zones Hwang, Il-Young Park, Chung Harrison, Kathleen Kehrl, John H. J Exp Med Article B lymphocyte–intrinsic Toll-like receptor (TLR) signals amplify humoral immunity and can exacerbate autoimmune diseases. We identify a new mechanism by which TLR signals may contribute to autoimmunity and chronic inflammation. We show that TLR4 signaling enhances B lymphocyte trafficking into lymph nodes (LNs), induces B lymphocyte clustering and interactions within LN follicles, leads to sustained in vivo B cell proliferation, overcomes the restriction that limits the access of nonantigen-activated B cells to germinal center dark zones, and enhances the generation of memory and plasma cells. Intravital microscopy and in vivo tracking studies of B cells transferred to recipient mice revealed that TLR4-activated, but not nonstimulated, B cells accumulated within the dark zones of preexisting germinal centers even when transferred with antigen-specific B cells. The TLR4-activated cells persist much better than nonstimulated cells, expanding both within the memory and plasma cell compartments. TLR-mediated activation of B cells may help to feed and stabilize the spontaneous and ectopic germinal centers that are so commonly found in autoimmune individuals and that accompany chronic inflammation. The Rockefeller University Press 2009-11-23 /pmc/articles/PMC2806604/ /pubmed/19917774 http://dx.doi.org/10.1084/jem.20091982 Text en © 2009 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.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Hwang, Il-Young Park, Chung Harrison, Kathleen Kehrl, John H. TLR4 signaling augments B lymphocyte migration and overcomes the restriction that limits access to germinal center dark zones |
title | TLR4 signaling augments B lymphocyte migration and overcomes the restriction that limits access to germinal center dark zones |
title_full | TLR4 signaling augments B lymphocyte migration and overcomes the restriction that limits access to germinal center dark zones |
title_fullStr | TLR4 signaling augments B lymphocyte migration and overcomes the restriction that limits access to germinal center dark zones |
title_full_unstemmed | TLR4 signaling augments B lymphocyte migration and overcomes the restriction that limits access to germinal center dark zones |
title_short | TLR4 signaling augments B lymphocyte migration and overcomes the restriction that limits access to germinal center dark zones |
title_sort | tlr4 signaling augments b lymphocyte migration and overcomes the restriction that limits access to germinal center dark zones |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806604/ https://www.ncbi.nlm.nih.gov/pubmed/19917774 http://dx.doi.org/10.1084/jem.20091982 |
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