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FK506-Binding Protein 11 Is a Novel Plasma Cell-Specific Antibody Folding Catalyst with Increased Expression in Idiopathic Pulmonary Fibrosis
Antibodies are central effectors of the adaptive immune response, widespread used therapeutics, but also potentially disease-causing biomolecules. Antibody folding catalysts in the plasma cell are incompletely defined. Idiopathic pulmonary fibrosis (IPF) is a fatal chronic lung disease with increasi...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027113/ https://www.ncbi.nlm.nih.gov/pubmed/35456020 http://dx.doi.org/10.3390/cells11081341 |
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author | Preisendörfer, Stefan Ishikawa, Yoshihiro Hennen, Elisabeth Winklmeier, Stephan Schupp, Jonas C. Knüppel, Larissa Fernandez, Isis E. Binzenhöfer, Leonhard Flatley, Andrew Juan-Guardela, Brenda M. Ruppert, Clemens Guenther, Andreas Frankenberger, Marion Hatz, Rudolf A. Kneidinger, Nikolaus Behr, Jürgen Feederle, Regina Schepers, Aloys Hilgendorff, Anne Kaminski, Naftali Meinl, Edgar Bächinger, Hans Peter Eickelberg, Oliver Staab-Weijnitz, Claudia A. |
author_facet | Preisendörfer, Stefan Ishikawa, Yoshihiro Hennen, Elisabeth Winklmeier, Stephan Schupp, Jonas C. Knüppel, Larissa Fernandez, Isis E. Binzenhöfer, Leonhard Flatley, Andrew Juan-Guardela, Brenda M. Ruppert, Clemens Guenther, Andreas Frankenberger, Marion Hatz, Rudolf A. Kneidinger, Nikolaus Behr, Jürgen Feederle, Regina Schepers, Aloys Hilgendorff, Anne Kaminski, Naftali Meinl, Edgar Bächinger, Hans Peter Eickelberg, Oliver Staab-Weijnitz, Claudia A. |
author_sort | Preisendörfer, Stefan |
collection | PubMed |
description | Antibodies are central effectors of the adaptive immune response, widespread used therapeutics, but also potentially disease-causing biomolecules. Antibody folding catalysts in the plasma cell are incompletely defined. Idiopathic pulmonary fibrosis (IPF) is a fatal chronic lung disease with increasingly recognized autoimmune features. We found elevated expression of FK506-binding protein 11 (FKBP11) in IPF lungs where FKBP11 specifically localized to antibody-producing plasma cells. Suggesting a general role in plasma cells, plasma cell-specific FKBP11 expression was equally observed in lymphatic tissues, and in vitro B cell to plasma cell differentiation was accompanied by induction of FKBP11 expression. Recombinant human FKBP11 was able to refold IgG antibody in vitro and inhibited by FK506, strongly supporting a function as antibody peptidyl-prolyl cis-trans isomerase. Induction of ER stress in cell lines demonstrated induction of FKBP11 in the context of the unfolded protein response in an X-box-binding protein 1 (XBP1)-dependent manner. While deficiency of FKBP11 increased susceptibility to ER stress-mediated cell death in an alveolar epithelial cell line, FKBP11 knockdown in an antibody-producing hybridoma cell line neither induced cell death nor decreased expression or secretion of IgG antibody. Similarly, antibody secretion by the same hybridoma cell line was not affected by knockdown of the established antibody peptidyl-prolyl isomerase cyclophilin B. The results are consistent with FKBP11 as a novel XBP1-regulated antibody peptidyl-prolyl cis-trans isomerase and indicate significant redundancy in the ER-resident folding machinery of antibody-producing hybridoma cells. |
format | Online Article Text |
id | pubmed-9027113 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90271132022-04-23 FK506-Binding Protein 11 Is a Novel Plasma Cell-Specific Antibody Folding Catalyst with Increased Expression in Idiopathic Pulmonary Fibrosis Preisendörfer, Stefan Ishikawa, Yoshihiro Hennen, Elisabeth Winklmeier, Stephan Schupp, Jonas C. Knüppel, Larissa Fernandez, Isis E. Binzenhöfer, Leonhard Flatley, Andrew Juan-Guardela, Brenda M. Ruppert, Clemens Guenther, Andreas Frankenberger, Marion Hatz, Rudolf A. Kneidinger, Nikolaus Behr, Jürgen Feederle, Regina Schepers, Aloys Hilgendorff, Anne Kaminski, Naftali Meinl, Edgar Bächinger, Hans Peter Eickelberg, Oliver Staab-Weijnitz, Claudia A. Cells Article Antibodies are central effectors of the adaptive immune response, widespread used therapeutics, but also potentially disease-causing biomolecules. Antibody folding catalysts in the plasma cell are incompletely defined. Idiopathic pulmonary fibrosis (IPF) is a fatal chronic lung disease with increasingly recognized autoimmune features. We found elevated expression of FK506-binding protein 11 (FKBP11) in IPF lungs where FKBP11 specifically localized to antibody-producing plasma cells. Suggesting a general role in plasma cells, plasma cell-specific FKBP11 expression was equally observed in lymphatic tissues, and in vitro B cell to plasma cell differentiation was accompanied by induction of FKBP11 expression. Recombinant human FKBP11 was able to refold IgG antibody in vitro and inhibited by FK506, strongly supporting a function as antibody peptidyl-prolyl cis-trans isomerase. Induction of ER stress in cell lines demonstrated induction of FKBP11 in the context of the unfolded protein response in an X-box-binding protein 1 (XBP1)-dependent manner. While deficiency of FKBP11 increased susceptibility to ER stress-mediated cell death in an alveolar epithelial cell line, FKBP11 knockdown in an antibody-producing hybridoma cell line neither induced cell death nor decreased expression or secretion of IgG antibody. Similarly, antibody secretion by the same hybridoma cell line was not affected by knockdown of the established antibody peptidyl-prolyl isomerase cyclophilin B. The results are consistent with FKBP11 as a novel XBP1-regulated antibody peptidyl-prolyl cis-trans isomerase and indicate significant redundancy in the ER-resident folding machinery of antibody-producing hybridoma cells. MDPI 2022-04-14 /pmc/articles/PMC9027113/ /pubmed/35456020 http://dx.doi.org/10.3390/cells11081341 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Preisendörfer, Stefan Ishikawa, Yoshihiro Hennen, Elisabeth Winklmeier, Stephan Schupp, Jonas C. Knüppel, Larissa Fernandez, Isis E. Binzenhöfer, Leonhard Flatley, Andrew Juan-Guardela, Brenda M. Ruppert, Clemens Guenther, Andreas Frankenberger, Marion Hatz, Rudolf A. Kneidinger, Nikolaus Behr, Jürgen Feederle, Regina Schepers, Aloys Hilgendorff, Anne Kaminski, Naftali Meinl, Edgar Bächinger, Hans Peter Eickelberg, Oliver Staab-Weijnitz, Claudia A. FK506-Binding Protein 11 Is a Novel Plasma Cell-Specific Antibody Folding Catalyst with Increased Expression in Idiopathic Pulmonary Fibrosis |
title | FK506-Binding Protein 11 Is a Novel Plasma Cell-Specific Antibody Folding Catalyst with Increased Expression in Idiopathic Pulmonary Fibrosis |
title_full | FK506-Binding Protein 11 Is a Novel Plasma Cell-Specific Antibody Folding Catalyst with Increased Expression in Idiopathic Pulmonary Fibrosis |
title_fullStr | FK506-Binding Protein 11 Is a Novel Plasma Cell-Specific Antibody Folding Catalyst with Increased Expression in Idiopathic Pulmonary Fibrosis |
title_full_unstemmed | FK506-Binding Protein 11 Is a Novel Plasma Cell-Specific Antibody Folding Catalyst with Increased Expression in Idiopathic Pulmonary Fibrosis |
title_short | FK506-Binding Protein 11 Is a Novel Plasma Cell-Specific Antibody Folding Catalyst with Increased Expression in Idiopathic Pulmonary Fibrosis |
title_sort | fk506-binding protein 11 is a novel plasma cell-specific antibody folding catalyst with increased expression in idiopathic pulmonary fibrosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027113/ https://www.ncbi.nlm.nih.gov/pubmed/35456020 http://dx.doi.org/10.3390/cells11081341 |
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