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Co-Expression of the B-Cell Key Transcription Factors Blimp-1 and IRF4 Identifies Plasma Cells in the Pig

Antibody-secreting plasma cells (PCs) have remained largely uncharacterized for years in the field of porcine immunology. For an in-depth study of porcine PCs, we identified cross-reactive antibodies against three key transcription factors: PR domain zinc finger protein-1 (Blimp-1), interferon regul...

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Autores principales: Villanueva-Hernández, Sonia, Adib Razavi, Mahsa, van Dongen, Katinka A., Stadler, Maria, de Luca, Karelle, Beyersdorf, Niklas, Saalmüller, Armin, Gerner, Wilhelm, Mair, Kerstin H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024106/
https://www.ncbi.nlm.nih.gov/pubmed/35464468
http://dx.doi.org/10.3389/fimmu.2022.854257
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author Villanueva-Hernández, Sonia
Adib Razavi, Mahsa
van Dongen, Katinka A.
Stadler, Maria
de Luca, Karelle
Beyersdorf, Niklas
Saalmüller, Armin
Gerner, Wilhelm
Mair, Kerstin H.
author_facet Villanueva-Hernández, Sonia
Adib Razavi, Mahsa
van Dongen, Katinka A.
Stadler, Maria
de Luca, Karelle
Beyersdorf, Niklas
Saalmüller, Armin
Gerner, Wilhelm
Mair, Kerstin H.
author_sort Villanueva-Hernández, Sonia
collection PubMed
description Antibody-secreting plasma cells (PCs) have remained largely uncharacterized for years in the field of porcine immunology. For an in-depth study of porcine PCs, we identified cross-reactive antibodies against three key transcription factors: PR domain zinc finger protein-1 (Blimp-1), interferon regulatory factor 4 (IRF4), and paired box 5 (Pax5). A distinct Blimp-1(+)IRF4(+) cell population was found in cells isolated from blood, spleen, lymph nodes, bone marrow, and lung of healthy pigs. These cells showed a downregulation of Pax5 compared to other B cells. Within Blimp-1(+)IRF4(+) B cells, IgM-, IgG-, and IgA-expressing cells were identified and immunoglobulin-class distribution was clearly different between the anatomical locations, with IgA(+) PCs dominating in lung tissue and IgM(+) PCs dominating in the spleen. Expression patterns of Ki-67, MHC-II, CD9, and CD28 were investigated in the different organs. A high expression of Ki-67 was observed in blood, suggesting a plasmablast stage. Blimp-1(+)IRF4(+) cells showed an overall lower expression of MHC-II compared to regular B cells, confirming a progressive loss in B-cell differentiation toward the PC stage. CD28 showed slightly elevated expression levels in Blimp-1(+)IRF4(+) cells in most organs, a phenotype that is also described for PCs in mice and humans. This was not seen for CD9. We further developed a FACS-sorting strategy for live porcine PCs for functional assays. CD3(-)CD16(-)CD172a(–) sorted cells with a CD49d(high)FSC-A(high) phenotype contained Blimp-1(+)IRF4(+) cells and were capable of spontaneous IgG production, thus confirming PC identity. These results reveal fundamental phenotypes of porcine PCs and will facilitate the study of this specific B-cell subset in the future.
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spelling pubmed-90241062022-04-23 Co-Expression of the B-Cell Key Transcription Factors Blimp-1 and IRF4 Identifies Plasma Cells in the Pig Villanueva-Hernández, Sonia Adib Razavi, Mahsa van Dongen, Katinka A. Stadler, Maria de Luca, Karelle Beyersdorf, Niklas Saalmüller, Armin Gerner, Wilhelm Mair, Kerstin H. Front Immunol Immunology Antibody-secreting plasma cells (PCs) have remained largely uncharacterized for years in the field of porcine immunology. For an in-depth study of porcine PCs, we identified cross-reactive antibodies against three key transcription factors: PR domain zinc finger protein-1 (Blimp-1), interferon regulatory factor 4 (IRF4), and paired box 5 (Pax5). A distinct Blimp-1(+)IRF4(+) cell population was found in cells isolated from blood, spleen, lymph nodes, bone marrow, and lung of healthy pigs. These cells showed a downregulation of Pax5 compared to other B cells. Within Blimp-1(+)IRF4(+) B cells, IgM-, IgG-, and IgA-expressing cells were identified and immunoglobulin-class distribution was clearly different between the anatomical locations, with IgA(+) PCs dominating in lung tissue and IgM(+) PCs dominating in the spleen. Expression patterns of Ki-67, MHC-II, CD9, and CD28 were investigated in the different organs. A high expression of Ki-67 was observed in blood, suggesting a plasmablast stage. Blimp-1(+)IRF4(+) cells showed an overall lower expression of MHC-II compared to regular B cells, confirming a progressive loss in B-cell differentiation toward the PC stage. CD28 showed slightly elevated expression levels in Blimp-1(+)IRF4(+) cells in most organs, a phenotype that is also described for PCs in mice and humans. This was not seen for CD9. We further developed a FACS-sorting strategy for live porcine PCs for functional assays. CD3(-)CD16(-)CD172a(–) sorted cells with a CD49d(high)FSC-A(high) phenotype contained Blimp-1(+)IRF4(+) cells and were capable of spontaneous IgG production, thus confirming PC identity. These results reveal fundamental phenotypes of porcine PCs and will facilitate the study of this specific B-cell subset in the future. Frontiers Media S.A. 2022-04-08 /pmc/articles/PMC9024106/ /pubmed/35464468 http://dx.doi.org/10.3389/fimmu.2022.854257 Text en Copyright © 2022 Villanueva-Hernández, Adib Razavi, van Dongen, Stadler, de Luca, Beyersdorf, Saalmüller, Gerner and Mair https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Villanueva-Hernández, Sonia
Adib Razavi, Mahsa
van Dongen, Katinka A.
Stadler, Maria
de Luca, Karelle
Beyersdorf, Niklas
Saalmüller, Armin
Gerner, Wilhelm
Mair, Kerstin H.
Co-Expression of the B-Cell Key Transcription Factors Blimp-1 and IRF4 Identifies Plasma Cells in the Pig
title Co-Expression of the B-Cell Key Transcription Factors Blimp-1 and IRF4 Identifies Plasma Cells in the Pig
title_full Co-Expression of the B-Cell Key Transcription Factors Blimp-1 and IRF4 Identifies Plasma Cells in the Pig
title_fullStr Co-Expression of the B-Cell Key Transcription Factors Blimp-1 and IRF4 Identifies Plasma Cells in the Pig
title_full_unstemmed Co-Expression of the B-Cell Key Transcription Factors Blimp-1 and IRF4 Identifies Plasma Cells in the Pig
title_short Co-Expression of the B-Cell Key Transcription Factors Blimp-1 and IRF4 Identifies Plasma Cells in the Pig
title_sort co-expression of the b-cell key transcription factors blimp-1 and irf4 identifies plasma cells in the pig
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9024106/
https://www.ncbi.nlm.nih.gov/pubmed/35464468
http://dx.doi.org/10.3389/fimmu.2022.854257
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