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High microbiota reactivity of adult human intestinal IgA requires somatic mutations

The gut is home to the body’s largest population of plasma cells. In healthy individuals, IgA is the dominating isotype, whereas patients with inflammatory bowel disease also produce high concentrations of IgG. In the gut lumen, secretory IgA binds pathogens and toxins but also the microbiota. Howev...

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Autores principales: Kabbert, Johanna, Benckert, Julia, Rollenske, Tim, Hitch, Thomas C.A., Clavel, Thomas, Cerovic, Vuk, Wardemann, Hedda, Pabst, Oliver
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526496/
https://www.ncbi.nlm.nih.gov/pubmed/32640466
http://dx.doi.org/10.1084/jem.20200275
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author Kabbert, Johanna
Benckert, Julia
Rollenske, Tim
Hitch, Thomas C.A.
Clavel, Thomas
Cerovic, Vuk
Wardemann, Hedda
Pabst, Oliver
author_facet Kabbert, Johanna
Benckert, Julia
Rollenske, Tim
Hitch, Thomas C.A.
Clavel, Thomas
Cerovic, Vuk
Wardemann, Hedda
Pabst, Oliver
author_sort Kabbert, Johanna
collection PubMed
description The gut is home to the body’s largest population of plasma cells. In healthy individuals, IgA is the dominating isotype, whereas patients with inflammatory bowel disease also produce high concentrations of IgG. In the gut lumen, secretory IgA binds pathogens and toxins but also the microbiota. However, the antigen specificity of IgA and IgG for the microbiota and underlying mechanisms of antibody binding to bacteria are largely unknown. Here we show that microbiota binding is a defining property of human intestinal antibodies in both healthy and inflamed gut. Some bacterial taxa were commonly targeted by different monoclonal antibodies, whereas others selectively bound single antibodies. Interestingly, individual human monoclonal antibodies from both healthy and inflamed intestines bound phylogenetically unrelated bacterial species. This microbiota cross-species reactivity did not correlate with antibody polyreactivity but was crucially dependent on the accumulation of somatic mutations. Therefore, our data suggest that a system of affinity-matured, microbiota cross-species–reactive IgA is a common aspect of SIgA–microbiota interactions in the gut.
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spelling pubmed-75264962020-10-07 High microbiota reactivity of adult human intestinal IgA requires somatic mutations Kabbert, Johanna Benckert, Julia Rollenske, Tim Hitch, Thomas C.A. Clavel, Thomas Cerovic, Vuk Wardemann, Hedda Pabst, Oliver J Exp Med Article The gut is home to the body’s largest population of plasma cells. In healthy individuals, IgA is the dominating isotype, whereas patients with inflammatory bowel disease also produce high concentrations of IgG. In the gut lumen, secretory IgA binds pathogens and toxins but also the microbiota. However, the antigen specificity of IgA and IgG for the microbiota and underlying mechanisms of antibody binding to bacteria are largely unknown. Here we show that microbiota binding is a defining property of human intestinal antibodies in both healthy and inflamed gut. Some bacterial taxa were commonly targeted by different monoclonal antibodies, whereas others selectively bound single antibodies. Interestingly, individual human monoclonal antibodies from both healthy and inflamed intestines bound phylogenetically unrelated bacterial species. This microbiota cross-species reactivity did not correlate with antibody polyreactivity but was crucially dependent on the accumulation of somatic mutations. Therefore, our data suggest that a system of affinity-matured, microbiota cross-species–reactive IgA is a common aspect of SIgA–microbiota interactions in the gut. Rockefeller University Press 2020-07-08 /pmc/articles/PMC7526496/ /pubmed/32640466 http://dx.doi.org/10.1084/jem.20200275 Text en © 2020 Kabbert et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kabbert, Johanna
Benckert, Julia
Rollenske, Tim
Hitch, Thomas C.A.
Clavel, Thomas
Cerovic, Vuk
Wardemann, Hedda
Pabst, Oliver
High microbiota reactivity of adult human intestinal IgA requires somatic mutations
title High microbiota reactivity of adult human intestinal IgA requires somatic mutations
title_full High microbiota reactivity of adult human intestinal IgA requires somatic mutations
title_fullStr High microbiota reactivity of adult human intestinal IgA requires somatic mutations
title_full_unstemmed High microbiota reactivity of adult human intestinal IgA requires somatic mutations
title_short High microbiota reactivity of adult human intestinal IgA requires somatic mutations
title_sort high microbiota reactivity of adult human intestinal iga requires somatic mutations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526496/
https://www.ncbi.nlm.nih.gov/pubmed/32640466
http://dx.doi.org/10.1084/jem.20200275
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