Cargando…

Antibody Reactivity of B Cells in Lupus Patients with Increased Disease Activity and ARID3a Expression

Earlier studies showed that the DNA-binding protein, Bright/ARID3a bound to a subset of human and mouse immunoglobulin heavy chain promoters where it enhanced expression. Indeed, mice with transgenic expression of ARID3a in all B lymphocytes have expanded MZ B cells and produce anti-nuclear antibodi...

Descripción completa

Detalles Bibliográficos
Autores principales: Ward, Julie M., James, Judith A., Zhao, Yan D., Webb, Carol F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451160/
https://www.ncbi.nlm.nih.gov/pubmed/28580178
http://dx.doi.org/10.3390/antib4040354
_version_ 1783240124536979456
author Ward, Julie M.
James, Judith A.
Zhao, Yan D.
Webb, Carol F.
author_facet Ward, Julie M.
James, Judith A.
Zhao, Yan D.
Webb, Carol F.
author_sort Ward, Julie M.
collection PubMed
description Earlier studies showed that the DNA-binding protein, Bright/ARID3a bound to a subset of human and mouse immunoglobulin heavy chain promoters where it enhanced expression. Indeed, mice with transgenic expression of ARID3a in all B lymphocytes have expanded MZ B cells and produce anti-nuclear antibodies (ANAs). Consistent with our findings in mice, we observed that human systemic lupus erythematosus (SLE) patients had expanded numbers of peripheral blood ARID3a(+) B cells that were associated with increased disease activity (p = 0.0038). We hypothesized that ARID3a(+) naïve B cells would eventually produce autoantibodies, explaining associations between ARID3a expression and disease activity in lupus. Unlike healthy controls, ARID3a was expressed in the naïve B cell population in SLE patients, and we hypothesized that these might represent expansions of autoreactive cells. Therefore, monoclonal antibodies were generated from single-sorted naïve B cells derived from patients with normal (ARID3a(N)) and high (ARID3a(H)) numbers of ARID3a(+) B cells. We found that ARID3a expression did not correlate with autoantibody expression. Furthermore, measures of antigen specificities of autoreactive antibodies did not reveal skewing toward particular proteins. These data suggest that the association of increased disease activity in SLE with numbers of ARID3a(+) B lymphocytes may be mediated by an antibody-independent mechanism.
format Online
Article
Text
id pubmed-5451160
institution National Center for Biotechnology Information
language English
publishDate 2015
record_format MEDLINE/PubMed
spelling pubmed-54511602017-05-31 Antibody Reactivity of B Cells in Lupus Patients with Increased Disease Activity and ARID3a Expression Ward, Julie M. James, Judith A. Zhao, Yan D. Webb, Carol F. Antibodies (Basel) Article Earlier studies showed that the DNA-binding protein, Bright/ARID3a bound to a subset of human and mouse immunoglobulin heavy chain promoters where it enhanced expression. Indeed, mice with transgenic expression of ARID3a in all B lymphocytes have expanded MZ B cells and produce anti-nuclear antibodies (ANAs). Consistent with our findings in mice, we observed that human systemic lupus erythematosus (SLE) patients had expanded numbers of peripheral blood ARID3a(+) B cells that were associated with increased disease activity (p = 0.0038). We hypothesized that ARID3a(+) naïve B cells would eventually produce autoantibodies, explaining associations between ARID3a expression and disease activity in lupus. Unlike healthy controls, ARID3a was expressed in the naïve B cell population in SLE patients, and we hypothesized that these might represent expansions of autoreactive cells. Therefore, monoclonal antibodies were generated from single-sorted naïve B cells derived from patients with normal (ARID3a(N)) and high (ARID3a(H)) numbers of ARID3a(+) B cells. We found that ARID3a expression did not correlate with autoantibody expression. Furthermore, measures of antigen specificities of autoreactive antibodies did not reveal skewing toward particular proteins. These data suggest that the association of increased disease activity in SLE with numbers of ARID3a(+) B lymphocytes may be mediated by an antibody-independent mechanism. 2015-11-17 2015-12 /pmc/articles/PMC5451160/ /pubmed/28580178 http://dx.doi.org/10.3390/antib4040354 Text en http://creativecommons.org/licenses/by/4.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ward, Julie M.
James, Judith A.
Zhao, Yan D.
Webb, Carol F.
Antibody Reactivity of B Cells in Lupus Patients with Increased Disease Activity and ARID3a Expression
title Antibody Reactivity of B Cells in Lupus Patients with Increased Disease Activity and ARID3a Expression
title_full Antibody Reactivity of B Cells in Lupus Patients with Increased Disease Activity and ARID3a Expression
title_fullStr Antibody Reactivity of B Cells in Lupus Patients with Increased Disease Activity and ARID3a Expression
title_full_unstemmed Antibody Reactivity of B Cells in Lupus Patients with Increased Disease Activity and ARID3a Expression
title_short Antibody Reactivity of B Cells in Lupus Patients with Increased Disease Activity and ARID3a Expression
title_sort antibody reactivity of b cells in lupus patients with increased disease activity and arid3a expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451160/
https://www.ncbi.nlm.nih.gov/pubmed/28580178
http://dx.doi.org/10.3390/antib4040354
work_keys_str_mv AT wardjuliem antibodyreactivityofbcellsinlupuspatientswithincreaseddiseaseactivityandarid3aexpression
AT jamesjuditha antibodyreactivityofbcellsinlupuspatientswithincreaseddiseaseactivityandarid3aexpression
AT zhaoyand antibodyreactivityofbcellsinlupuspatientswithincreaseddiseaseactivityandarid3aexpression
AT webbcarolf antibodyreactivityofbcellsinlupuspatientswithincreaseddiseaseactivityandarid3aexpression