Cargando…

Serum from patients with SLE instructs monocytes to promote IgG and IgA plasmablast differentiation

The development of autoantibodies is a hallmark of systemic lupus erythematosus (SLE). SLE serum can induce monocyte differentiation into dendritic cells (DCs) in a type I IFN–dependent manner. Such SLE-DCs activate T cells, but whether they promote B cell responses is not known. In this study, we d...

Descripción completa

Detalles Bibliográficos
Autores principales: Joo, HyeMee, Coquery, Christine, Xue, Yaming, Gayet, Ingrid, Dillon, Stacey R., Punaro, Marilynn, Zurawski, Gerard, Banchereau, Jacques, Pascual, Virginia, Oh, SangKon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405503/
https://www.ncbi.nlm.nih.gov/pubmed/22689824
http://dx.doi.org/10.1084/jem.20111644
_version_ 1782239148939149312
author Joo, HyeMee
Coquery, Christine
Xue, Yaming
Gayet, Ingrid
Dillon, Stacey R.
Punaro, Marilynn
Zurawski, Gerard
Banchereau, Jacques
Pascual, Virginia
Oh, SangKon
author_facet Joo, HyeMee
Coquery, Christine
Xue, Yaming
Gayet, Ingrid
Dillon, Stacey R.
Punaro, Marilynn
Zurawski, Gerard
Banchereau, Jacques
Pascual, Virginia
Oh, SangKon
author_sort Joo, HyeMee
collection PubMed
description The development of autoantibodies is a hallmark of systemic lupus erythematosus (SLE). SLE serum can induce monocyte differentiation into dendritic cells (DCs) in a type I IFN–dependent manner. Such SLE-DCs activate T cells, but whether they promote B cell responses is not known. In this study, we demonstrate that SLE-DCs can efficiently stimulate naive and memory B cells to differentiate into IgG- and IgA-plasmablasts (PBs) resembling those found in the blood of SLE patients. SLE-DC–mediated IgG-PB differentiation is dependent on B cell–activating factor (BAFF) and IL-10, whereas IgA-PB differentiation is dependent on a proliferation-inducing ligand (APRIL). Importantly, SLE-DCs express CD138 and trans-present CD138-bound APRIL to B cells, leading to the induction of IgA switching and PB differentiation in an IFN-α–independent manner. We further found that this mechanism of providing B cell help is relevant in vivo, as CD138-bound APRIL is expressed on blood monocytes from active SLE patients. Collectively, our study suggests that a direct myeloid DC–B cell interplay might contribute to the pathogenesis of SLE.
format Online
Article
Text
id pubmed-3405503
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-34055032013-01-02 Serum from patients with SLE instructs monocytes to promote IgG and IgA plasmablast differentiation Joo, HyeMee Coquery, Christine Xue, Yaming Gayet, Ingrid Dillon, Stacey R. Punaro, Marilynn Zurawski, Gerard Banchereau, Jacques Pascual, Virginia Oh, SangKon J Exp Med Article The development of autoantibodies is a hallmark of systemic lupus erythematosus (SLE). SLE serum can induce monocyte differentiation into dendritic cells (DCs) in a type I IFN–dependent manner. Such SLE-DCs activate T cells, but whether they promote B cell responses is not known. In this study, we demonstrate that SLE-DCs can efficiently stimulate naive and memory B cells to differentiate into IgG- and IgA-plasmablasts (PBs) resembling those found in the blood of SLE patients. SLE-DC–mediated IgG-PB differentiation is dependent on B cell–activating factor (BAFF) and IL-10, whereas IgA-PB differentiation is dependent on a proliferation-inducing ligand (APRIL). Importantly, SLE-DCs express CD138 and trans-present CD138-bound APRIL to B cells, leading to the induction of IgA switching and PB differentiation in an IFN-α–independent manner. We further found that this mechanism of providing B cell help is relevant in vivo, as CD138-bound APRIL is expressed on blood monocytes from active SLE patients. Collectively, our study suggests that a direct myeloid DC–B cell interplay might contribute to the pathogenesis of SLE. The Rockefeller University Press 2012-07-02 /pmc/articles/PMC3405503/ /pubmed/22689824 http://dx.doi.org/10.1084/jem.20111644 Text en © 2012 Joo et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Joo, HyeMee
Coquery, Christine
Xue, Yaming
Gayet, Ingrid
Dillon, Stacey R.
Punaro, Marilynn
Zurawski, Gerard
Banchereau, Jacques
Pascual, Virginia
Oh, SangKon
Serum from patients with SLE instructs monocytes to promote IgG and IgA plasmablast differentiation
title Serum from patients with SLE instructs monocytes to promote IgG and IgA plasmablast differentiation
title_full Serum from patients with SLE instructs monocytes to promote IgG and IgA plasmablast differentiation
title_fullStr Serum from patients with SLE instructs monocytes to promote IgG and IgA plasmablast differentiation
title_full_unstemmed Serum from patients with SLE instructs monocytes to promote IgG and IgA plasmablast differentiation
title_short Serum from patients with SLE instructs monocytes to promote IgG and IgA plasmablast differentiation
title_sort serum from patients with sle instructs monocytes to promote igg and iga plasmablast differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405503/
https://www.ncbi.nlm.nih.gov/pubmed/22689824
http://dx.doi.org/10.1084/jem.20111644
work_keys_str_mv AT joohyemee serumfrompatientswithsleinstructsmonocytestopromoteiggandigaplasmablastdifferentiation
AT coquerychristine serumfrompatientswithsleinstructsmonocytestopromoteiggandigaplasmablastdifferentiation
AT xueyaming serumfrompatientswithsleinstructsmonocytestopromoteiggandigaplasmablastdifferentiation
AT gayetingrid serumfrompatientswithsleinstructsmonocytestopromoteiggandigaplasmablastdifferentiation
AT dillonstaceyr serumfrompatientswithsleinstructsmonocytestopromoteiggandigaplasmablastdifferentiation
AT punaromarilynn serumfrompatientswithsleinstructsmonocytestopromoteiggandigaplasmablastdifferentiation
AT zurawskigerard serumfrompatientswithsleinstructsmonocytestopromoteiggandigaplasmablastdifferentiation
AT banchereaujacques serumfrompatientswithsleinstructsmonocytestopromoteiggandigaplasmablastdifferentiation
AT pascualvirginia serumfrompatientswithsleinstructsmonocytestopromoteiggandigaplasmablastdifferentiation
AT ohsangkon serumfrompatientswithsleinstructsmonocytestopromoteiggandigaplasmablastdifferentiation