Persistent autoantibody-production by intermediates between short-and long-lived plasma cells in inflamed lymph nodes of experimental epidermolysis bullosa acquisita.

Autoantibodies are believed to be maintained by either the continuous generation of short-lived plasma cells in secondary lymphoid tissues or by long-lived plasma cells localized in bone marrow and spleen. Here, we show in a mouse model for the autoimmune blistering skin disease epidermolysis bullos...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Benjamin Tiburzy, Martin Szyska, Hiroaki Iwata, Navina Chrobok, Upasana Kulkarni, Misa Hirose, Ralf J Ludwig, Kathrin Kalies, Jürgen Westermann, David Wong, Rudolf Armin Manz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b69bedf208664ce085a7c7d464091d60
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b69bedf208664ce085a7c7d464091d60
record_format	dspace
spelling	oai:doaj.org-article:b69bedf208664ce085a7c7d464091d602021-11-18T08:40:20ZPersistent autoantibody-production by intermediates between short-and long-lived plasma cells in inflamed lymph nodes of experimental epidermolysis bullosa acquisita.1932-620310.1371/journal.pone.0083631https://doaj.org/article/b69bedf208664ce085a7c7d464091d602013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24386241/?tool=EBIhttps://doaj.org/toc/1932-6203Autoantibodies are believed to be maintained by either the continuous generation of short-lived plasma cells in secondary lymphoid tissues or by long-lived plasma cells localized in bone marrow and spleen. Here, we show in a mouse model for the autoimmune blistering skin disease epidermolysis bullosa acquisita (EBA) that chronic autoantibody production can also be maintained in inflamed lymph nodes, by plasma cells exhibiting intermediate lifetimes. After EBA induction by immunization with a mCOL7c-GST-fusion protein, antigen-specific plasma cells and CD4 T cells were analyzed. Plasma cells were maintained for months in stable numbers in the draining lymph nodes, but not in spleen and bone marrow. In contrast, localization of mCOL7c-GST -specific CD4 T cells was not restricted to lymph nodes, indicating that availability of T cell help does not limit plasma cell localization to this site. BrdU-incorporation studies indicated that pathogenic mCOL7c- and non-pathogenic GST-specific plasma cells resemble intermediates between short-and long-lived plasma cells with half-lives of about 7 weeks. Immunization with mCOL7c-GST also yielded considerable numbers of plasma cells neither specific for mCOL7c- nor GST. These bystander-activated plasma cells exhibited much shorter half-lives and higher population turnover, suggesting that plasma cell lifetimes were only partly determined by the lymph node environment but also by the mode of activation. These results indicate that inflamed lymph nodes can harbor pathogenic plasma cells exhibiting distinct properties and hence may resemble a so far neglected site for chronic autoantibody production.Benjamin TiburzyMartin SzyskaHiroaki IwataNavina ChrobokUpasana KulkarniMisa HiroseRalf J LudwigKathrin KaliesJürgen WestermannDavid WongRudolf Armin ManzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e83631 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Benjamin Tiburzy Martin Szyska Hiroaki Iwata Navina Chrobok Upasana Kulkarni Misa Hirose Ralf J Ludwig Kathrin Kalies Jürgen Westermann David Wong Rudolf Armin Manz Persistent autoantibody-production by intermediates between short-and long-lived plasma cells in inflamed lymph nodes of experimental epidermolysis bullosa acquisita.
description	Autoantibodies are believed to be maintained by either the continuous generation of short-lived plasma cells in secondary lymphoid tissues or by long-lived plasma cells localized in bone marrow and spleen. Here, we show in a mouse model for the autoimmune blistering skin disease epidermolysis bullosa acquisita (EBA) that chronic autoantibody production can also be maintained in inflamed lymph nodes, by plasma cells exhibiting intermediate lifetimes. After EBA induction by immunization with a mCOL7c-GST-fusion protein, antigen-specific plasma cells and CD4 T cells were analyzed. Plasma cells were maintained for months in stable numbers in the draining lymph nodes, but not in spleen and bone marrow. In contrast, localization of mCOL7c-GST -specific CD4 T cells was not restricted to lymph nodes, indicating that availability of T cell help does not limit plasma cell localization to this site. BrdU-incorporation studies indicated that pathogenic mCOL7c- and non-pathogenic GST-specific plasma cells resemble intermediates between short-and long-lived plasma cells with half-lives of about 7 weeks. Immunization with mCOL7c-GST also yielded considerable numbers of plasma cells neither specific for mCOL7c- nor GST. These bystander-activated plasma cells exhibited much shorter half-lives and higher population turnover, suggesting that plasma cell lifetimes were only partly determined by the lymph node environment but also by the mode of activation. These results indicate that inflamed lymph nodes can harbor pathogenic plasma cells exhibiting distinct properties and hence may resemble a so far neglected site for chronic autoantibody production.
format	article
author	Benjamin Tiburzy Martin Szyska Hiroaki Iwata Navina Chrobok Upasana Kulkarni Misa Hirose Ralf J Ludwig Kathrin Kalies Jürgen Westermann David Wong Rudolf Armin Manz
author_facet	Benjamin Tiburzy Martin Szyska Hiroaki Iwata Navina Chrobok Upasana Kulkarni Misa Hirose Ralf J Ludwig Kathrin Kalies Jürgen Westermann David Wong Rudolf Armin Manz
author_sort	Benjamin Tiburzy
title	Persistent autoantibody-production by intermediates between short-and long-lived plasma cells in inflamed lymph nodes of experimental epidermolysis bullosa acquisita.
title_short	Persistent autoantibody-production by intermediates between short-and long-lived plasma cells in inflamed lymph nodes of experimental epidermolysis bullosa acquisita.
title_full	Persistent autoantibody-production by intermediates between short-and long-lived plasma cells in inflamed lymph nodes of experimental epidermolysis bullosa acquisita.
title_fullStr	Persistent autoantibody-production by intermediates between short-and long-lived plasma cells in inflamed lymph nodes of experimental epidermolysis bullosa acquisita.
title_full_unstemmed	Persistent autoantibody-production by intermediates between short-and long-lived plasma cells in inflamed lymph nodes of experimental epidermolysis bullosa acquisita.
title_sort	persistent autoantibody-production by intermediates between short-and long-lived plasma cells in inflamed lymph nodes of experimental epidermolysis bullosa acquisita.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/b69bedf208664ce085a7c7d464091d60
work_keys_str_mv	AT benjamintiburzy persistentautoantibodyproductionbyintermediatesbetweenshortandlonglivedplasmacellsininflamedlymphnodesofexperimentalepidermolysisbullosaacquisita AT martinszyska persistentautoantibodyproductionbyintermediatesbetweenshortandlonglivedplasmacellsininflamedlymphnodesofexperimentalepidermolysisbullosaacquisita AT hiroakiiwata persistentautoantibodyproductionbyintermediatesbetweenshortandlonglivedplasmacellsininflamedlymphnodesofexperimentalepidermolysisbullosaacquisita AT navinachrobok persistentautoantibodyproductionbyintermediatesbetweenshortandlonglivedplasmacellsininflamedlymphnodesofexperimentalepidermolysisbullosaacquisita AT upasanakulkarni persistentautoantibodyproductionbyintermediatesbetweenshortandlonglivedplasmacellsininflamedlymphnodesofexperimentalepidermolysisbullosaacquisita AT misahirose persistentautoantibodyproductionbyintermediatesbetweenshortandlonglivedplasmacellsininflamedlymphnodesofexperimentalepidermolysisbullosaacquisita AT ralfjludwig persistentautoantibodyproductionbyintermediatesbetweenshortandlonglivedplasmacellsininflamedlymphnodesofexperimentalepidermolysisbullosaacquisita AT kathrinkalies persistentautoantibodyproductionbyintermediatesbetweenshortandlonglivedplasmacellsininflamedlymphnodesofexperimentalepidermolysisbullosaacquisita AT jurgenwestermann persistentautoantibodyproductionbyintermediatesbetweenshortandlonglivedplasmacellsininflamedlymphnodesofexperimentalepidermolysisbullosaacquisita AT davidwong persistentautoantibodyproductionbyintermediatesbetweenshortandlonglivedplasmacellsininflamedlymphnodesofexperimentalepidermolysisbullosaacquisita AT rudolfarminmanz persistentautoantibodyproductionbyintermediatesbetweenshortandlonglivedplasmacellsininflamedlymphnodesofexperimentalepidermolysisbullosaacquisita
_version_	1718421465194299392

Persistent autoantibody-production by intermediates between short-and long-lived plasma cells in inflamed lymph nodes of experimental epidermolysis bullosa acquisita.

Ejemplares similares