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Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

Anti-lipid IgG antibodies are produced in some mycobacterial infections and in certain autoimmune diseases [such as anti-phospholipid syndrome, systemic lupus erythematosus (SLE)]. However, few studies have addressed the B cell responses underlying the production of these immunoglobulins. Anti-lipid...

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Autores principales: Wong-Baeza, Carlos, Reséndiz-Mora, Albany, Donis-Maturano, Luis, Wong-Baeza, Isabel, Zárate-Neira, Luz, Yam-Puc, Juan Carlos, Calderón-Amador, Juana, Medina, Yolanda, Wong, Carlos, Baeza, Isabel, Flores-Romo, Leopoldo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040728/
https://www.ncbi.nlm.nih.gov/pubmed/27746783
http://dx.doi.org/10.3389/fimmu.2016.00396
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author Wong-Baeza, Carlos
Reséndiz-Mora, Albany
Donis-Maturano, Luis
Wong-Baeza, Isabel
Zárate-Neira, Luz
Yam-Puc, Juan Carlos
Calderón-Amador, Juana
Medina, Yolanda
Wong, Carlos
Baeza, Isabel
Flores-Romo, Leopoldo
author_facet Wong-Baeza, Carlos
Reséndiz-Mora, Albany
Donis-Maturano, Luis
Wong-Baeza, Isabel
Zárate-Neira, Luz
Yam-Puc, Juan Carlos
Calderón-Amador, Juana
Medina, Yolanda
Wong, Carlos
Baeza, Isabel
Flores-Romo, Leopoldo
author_sort Wong-Baeza, Carlos
collection PubMed
description Anti-lipid IgG antibodies are produced in some mycobacterial infections and in certain autoimmune diseases [such as anti-phospholipid syndrome, systemic lupus erythematosus (SLE)]. However, few studies have addressed the B cell responses underlying the production of these immunoglobulins. Anti-lipid IgG antibodies are consistently found in a murine model resembling human lupus induced by chlorpromazine-stabilized non-bilayer phospholipid arrangements (NPA). NPA are transitory lipid associations found in the membranes of most cells; when NPA are stabilized they can become immunogenic and induce specific IgG antibodies, which appear to be involved in the development of the mouse model of lupus. Of note, anti-NPA antibodies are also detected in patients with SLE and leprosy. We used this model of lupus to investigate in vivo the cellular mechanisms that lead to the production of anti-lipid, class-switched IgG antibodies. In this murine lupus model, we found plasma cells (Gr1(−), CD19(−), CD138(+)) producing NPA-specific IgGs in the draining lymph nodes, the spleen, and the bone marrow. We also found a significant number of germinal center B cells (IgD(−), CD19(+), PNA(+)) specific for NPA in the draining lymph nodes and the spleen, and we identified in situ the presence of NPA in these germinal centers. By contrast, very few NPA-specific, extrafollicular reaction B cells (B220(+), Blimp1(+)) were found. Moreover, when assessing the anti-NPA IgG antibodies produced during the experimental protocol, we found that the affinity of these antibodies progressively increased over time. Altogether, our data indicate that, in this murine model resembling human lupus, B cells produce anti-NPA IgG antibodies mainly via germinal centers.
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spelling pubmed-50407282016-10-14 Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus Wong-Baeza, Carlos Reséndiz-Mora, Albany Donis-Maturano, Luis Wong-Baeza, Isabel Zárate-Neira, Luz Yam-Puc, Juan Carlos Calderón-Amador, Juana Medina, Yolanda Wong, Carlos Baeza, Isabel Flores-Romo, Leopoldo Front Immunol Immunology Anti-lipid IgG antibodies are produced in some mycobacterial infections and in certain autoimmune diseases [such as anti-phospholipid syndrome, systemic lupus erythematosus (SLE)]. However, few studies have addressed the B cell responses underlying the production of these immunoglobulins. Anti-lipid IgG antibodies are consistently found in a murine model resembling human lupus induced by chlorpromazine-stabilized non-bilayer phospholipid arrangements (NPA). NPA are transitory lipid associations found in the membranes of most cells; when NPA are stabilized they can become immunogenic and induce specific IgG antibodies, which appear to be involved in the development of the mouse model of lupus. Of note, anti-NPA antibodies are also detected in patients with SLE and leprosy. We used this model of lupus to investigate in vivo the cellular mechanisms that lead to the production of anti-lipid, class-switched IgG antibodies. In this murine lupus model, we found plasma cells (Gr1(−), CD19(−), CD138(+)) producing NPA-specific IgGs in the draining lymph nodes, the spleen, and the bone marrow. We also found a significant number of germinal center B cells (IgD(−), CD19(+), PNA(+)) specific for NPA in the draining lymph nodes and the spleen, and we identified in situ the presence of NPA in these germinal centers. By contrast, very few NPA-specific, extrafollicular reaction B cells (B220(+), Blimp1(+)) were found. Moreover, when assessing the anti-NPA IgG antibodies produced during the experimental protocol, we found that the affinity of these antibodies progressively increased over time. Altogether, our data indicate that, in this murine model resembling human lupus, B cells produce anti-NPA IgG antibodies mainly via germinal centers. Frontiers Media S.A. 2016-09-29 /pmc/articles/PMC5040728/ /pubmed/27746783 http://dx.doi.org/10.3389/fimmu.2016.00396 Text en Copyright © 2016 Wong-Baeza, Reséndiz-Mora, Donis-Maturano, Wong-Baeza, Zárate-Neira, Yam-Puc, Calderón-Amador, Medina, Wong, Baeza and Flores-Romo. http://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) or licensor 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
Wong-Baeza, Carlos
Reséndiz-Mora, Albany
Donis-Maturano, Luis
Wong-Baeza, Isabel
Zárate-Neira, Luz
Yam-Puc, Juan Carlos
Calderón-Amador, Juana
Medina, Yolanda
Wong, Carlos
Baeza, Isabel
Flores-Romo, Leopoldo
Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus
title Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus
title_full Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus
title_fullStr Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus
title_full_unstemmed Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus
title_short Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus
title_sort anti-lipid igg antibodies are produced via germinal centers in a murine model resembling human lupus
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5040728/
https://www.ncbi.nlm.nih.gov/pubmed/27746783
http://dx.doi.org/10.3389/fimmu.2016.00396
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