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Investigating the importance of B cells and antibodies during Trichuris muris infection using the IgMi mouse

ABSTRACT: The IgMi mouse has normal B cell development; its B cells express an IgM B cell receptor but cannot class switch or secrete antibody. Thus, the IgMi mouse offers a model system by which to dissect out antibody-dependent and antibody-independent B cell function. Here, we provide the first d...

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Autores principales: Sahputra, Rinal, Murphy, Emma A, Forman, Ruth, Mair, Iris, Fadlullah, Muhammad Z. H., Waisman, Ari, Muller, Werner, Else, Kathryn J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447682/
https://www.ncbi.nlm.nih.gov/pubmed/32778925
http://dx.doi.org/10.1007/s00109-020-01954-3
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author Sahputra, Rinal
Murphy, Emma A
Forman, Ruth
Mair, Iris
Fadlullah, Muhammad Z. H.
Waisman, Ari
Muller, Werner
Else, Kathryn J.
author_facet Sahputra, Rinal
Murphy, Emma A
Forman, Ruth
Mair, Iris
Fadlullah, Muhammad Z. H.
Waisman, Ari
Muller, Werner
Else, Kathryn J.
author_sort Sahputra, Rinal
collection PubMed
description ABSTRACT: The IgMi mouse has normal B cell development; its B cells express an IgM B cell receptor but cannot class switch or secrete antibody. Thus, the IgMi mouse offers a model system by which to dissect out antibody-dependent and antibody-independent B cell function. Here, we provide the first detailed characterisation of the IgMi mouse post-Trichuris muris (T. muris) infection, describing expulsion phenotype, cytokine production, gut pathology and changes in T regulatory cells, T follicular helper cells and germinal centre B cells, in addition to RNA sequencing (RNA seq) analyses of wild-type littermates (WT) and mutant B cells prior to and post infection. IgMi mice were susceptible to a high-dose infection, with reduced Th2 cytokines and elevated B cell-derived IL-10 in mesenteric lymph nodes (MLN) compared to controls. A low-dose infection regime revealed IgMi mice to have significantly more apoptotic cells in the gut compared to WT mice, but no change in intestinal inflammation. IL-10 levels were again elevated. Collectively, this study showcases the potential of the IgMi mouse as a tool for understanding B cell biology and suggests that the B cell plays both antibody-dependent and antibody-independent roles post high- and low-dose T. muris infection. KEY MESSAGES: During a high-dose T. muris infection, B cells are important in maintaining the Th1/Th2 balance in the MLN through an antibody-independent mechanism. High levels of IL-10 in the MLN early post-infection, and the presence of IL-10-producing B cells, correlates with susceptibility to T. muris infection. B cells maintain gut homeostasis during chronic T. muris infection via an antibody-dependent mechanism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00109-020-01954-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-74476822020-09-02 Investigating the importance of B cells and antibodies during Trichuris muris infection using the IgMi mouse Sahputra, Rinal Murphy, Emma A Forman, Ruth Mair, Iris Fadlullah, Muhammad Z. H. Waisman, Ari Muller, Werner Else, Kathryn J. J Mol Med (Berl) Original Article ABSTRACT: The IgMi mouse has normal B cell development; its B cells express an IgM B cell receptor but cannot class switch or secrete antibody. Thus, the IgMi mouse offers a model system by which to dissect out antibody-dependent and antibody-independent B cell function. Here, we provide the first detailed characterisation of the IgMi mouse post-Trichuris muris (T. muris) infection, describing expulsion phenotype, cytokine production, gut pathology and changes in T regulatory cells, T follicular helper cells and germinal centre B cells, in addition to RNA sequencing (RNA seq) analyses of wild-type littermates (WT) and mutant B cells prior to and post infection. IgMi mice were susceptible to a high-dose infection, with reduced Th2 cytokines and elevated B cell-derived IL-10 in mesenteric lymph nodes (MLN) compared to controls. A low-dose infection regime revealed IgMi mice to have significantly more apoptotic cells in the gut compared to WT mice, but no change in intestinal inflammation. IL-10 levels were again elevated. Collectively, this study showcases the potential of the IgMi mouse as a tool for understanding B cell biology and suggests that the B cell plays both antibody-dependent and antibody-independent roles post high- and low-dose T. muris infection. KEY MESSAGES: During a high-dose T. muris infection, B cells are important in maintaining the Th1/Th2 balance in the MLN through an antibody-independent mechanism. High levels of IL-10 in the MLN early post-infection, and the presence of IL-10-producing B cells, correlates with susceptibility to T. muris infection. B cells maintain gut homeostasis during chronic T. muris infection via an antibody-dependent mechanism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00109-020-01954-3) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-08-10 2020 /pmc/articles/PMC7447682/ /pubmed/32778925 http://dx.doi.org/10.1007/s00109-020-01954-3 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Original Article
Sahputra, Rinal
Murphy, Emma A
Forman, Ruth
Mair, Iris
Fadlullah, Muhammad Z. H.
Waisman, Ari
Muller, Werner
Else, Kathryn J.
Investigating the importance of B cells and antibodies during Trichuris muris infection using the IgMi mouse
title Investigating the importance of B cells and antibodies during Trichuris muris infection using the IgMi mouse
title_full Investigating the importance of B cells and antibodies during Trichuris muris infection using the IgMi mouse
title_fullStr Investigating the importance of B cells and antibodies during Trichuris muris infection using the IgMi mouse
title_full_unstemmed Investigating the importance of B cells and antibodies during Trichuris muris infection using the IgMi mouse
title_short Investigating the importance of B cells and antibodies during Trichuris muris infection using the IgMi mouse
title_sort investigating the importance of b cells and antibodies during trichuris muris infection using the igmi mouse
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447682/
https://www.ncbi.nlm.nih.gov/pubmed/32778925
http://dx.doi.org/10.1007/s00109-020-01954-3
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