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Atypical chemokine receptor 4 shapes activated B cell fate

Activated B cells can initially differentiate into three functionally distinct fates—early plasmablasts (PBs), germinal center (GC) B cells, or early memory B cells—by mechanisms that remain poorly understood. Here, we identify atypical chemokine receptor 4 (ACKR4), a decoy receptor that binds and d...

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Autores principales: Kara, Ervin E., Bastow, Cameron R., McKenzie, Duncan R., Gregor, Carly E., Fenix, Kevin A., Babb, Rachelle, Norton, Todd S., Zotos, Dimitra, Rodda, Lauren B., Hermes, Jana R., Bourne, Katherine, Gilchrist, Derek S., Nibbs, Robert J., Alsharifi, Mohammed, Vinuesa, Carola G., Tarlinton, David M., Brink, Robert, Hill, Geoffrey R., Cyster, Jason G., Comerford, Iain, McColl, Shaun R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839757/
https://www.ncbi.nlm.nih.gov/pubmed/29386231
http://dx.doi.org/10.1084/jem.20171067
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author Kara, Ervin E.
Bastow, Cameron R.
McKenzie, Duncan R.
Gregor, Carly E.
Fenix, Kevin A.
Babb, Rachelle
Norton, Todd S.
Zotos, Dimitra
Rodda, Lauren B.
Hermes, Jana R.
Bourne, Katherine
Gilchrist, Derek S.
Nibbs, Robert J.
Alsharifi, Mohammed
Vinuesa, Carola G.
Tarlinton, David M.
Brink, Robert
Hill, Geoffrey R.
Cyster, Jason G.
Comerford, Iain
McColl, Shaun R.
author_facet Kara, Ervin E.
Bastow, Cameron R.
McKenzie, Duncan R.
Gregor, Carly E.
Fenix, Kevin A.
Babb, Rachelle
Norton, Todd S.
Zotos, Dimitra
Rodda, Lauren B.
Hermes, Jana R.
Bourne, Katherine
Gilchrist, Derek S.
Nibbs, Robert J.
Alsharifi, Mohammed
Vinuesa, Carola G.
Tarlinton, David M.
Brink, Robert
Hill, Geoffrey R.
Cyster, Jason G.
Comerford, Iain
McColl, Shaun R.
author_sort Kara, Ervin E.
collection PubMed
description Activated B cells can initially differentiate into three functionally distinct fates—early plasmablasts (PBs), germinal center (GC) B cells, or early memory B cells—by mechanisms that remain poorly understood. Here, we identify atypical chemokine receptor 4 (ACKR4), a decoy receptor that binds and degrades CCR7 ligands CCL19/CCL21, as a regulator of early activated B cell differentiation. By restricting initial access to splenic interfollicular zones (IFZs), ACKR4 limits the early proliferation of activated B cells, reducing the numbers available for subsequent differentiation. Consequently, ACKR4 deficiency enhanced early PB and GC B cell responses in a CCL19/CCL21-dependent and B cell–intrinsic manner. Conversely, aberrant localization of ACKR4-deficient activated B cells to the IFZ was associated with their preferential commitment to the early PB linage. Our results reveal a regulatory mechanism of B cell trafficking via an atypical chemokine receptor that shapes activated B cell fate.
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spelling pubmed-58397572018-09-05 Atypical chemokine receptor 4 shapes activated B cell fate Kara, Ervin E. Bastow, Cameron R. McKenzie, Duncan R. Gregor, Carly E. Fenix, Kevin A. Babb, Rachelle Norton, Todd S. Zotos, Dimitra Rodda, Lauren B. Hermes, Jana R. Bourne, Katherine Gilchrist, Derek S. Nibbs, Robert J. Alsharifi, Mohammed Vinuesa, Carola G. Tarlinton, David M. Brink, Robert Hill, Geoffrey R. Cyster, Jason G. Comerford, Iain McColl, Shaun R. J Exp Med Research Articles Activated B cells can initially differentiate into three functionally distinct fates—early plasmablasts (PBs), germinal center (GC) B cells, or early memory B cells—by mechanisms that remain poorly understood. Here, we identify atypical chemokine receptor 4 (ACKR4), a decoy receptor that binds and degrades CCR7 ligands CCL19/CCL21, as a regulator of early activated B cell differentiation. By restricting initial access to splenic interfollicular zones (IFZs), ACKR4 limits the early proliferation of activated B cells, reducing the numbers available for subsequent differentiation. Consequently, ACKR4 deficiency enhanced early PB and GC B cell responses in a CCL19/CCL21-dependent and B cell–intrinsic manner. Conversely, aberrant localization of ACKR4-deficient activated B cells to the IFZ was associated with their preferential commitment to the early PB linage. Our results reveal a regulatory mechanism of B cell trafficking via an atypical chemokine receptor that shapes activated B cell fate. Rockefeller University Press 2018-03-05 /pmc/articles/PMC5839757/ /pubmed/29386231 http://dx.doi.org/10.1084/jem.20171067 Text en © 2018 Kara et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/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 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Kara, Ervin E.
Bastow, Cameron R.
McKenzie, Duncan R.
Gregor, Carly E.
Fenix, Kevin A.
Babb, Rachelle
Norton, Todd S.
Zotos, Dimitra
Rodda, Lauren B.
Hermes, Jana R.
Bourne, Katherine
Gilchrist, Derek S.
Nibbs, Robert J.
Alsharifi, Mohammed
Vinuesa, Carola G.
Tarlinton, David M.
Brink, Robert
Hill, Geoffrey R.
Cyster, Jason G.
Comerford, Iain
McColl, Shaun R.
Atypical chemokine receptor 4 shapes activated B cell fate
title Atypical chemokine receptor 4 shapes activated B cell fate
title_full Atypical chemokine receptor 4 shapes activated B cell fate
title_fullStr Atypical chemokine receptor 4 shapes activated B cell fate
title_full_unstemmed Atypical chemokine receptor 4 shapes activated B cell fate
title_short Atypical chemokine receptor 4 shapes activated B cell fate
title_sort atypical chemokine receptor 4 shapes activated b cell fate
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839757/
https://www.ncbi.nlm.nih.gov/pubmed/29386231
http://dx.doi.org/10.1084/jem.20171067
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