Investigating the importance of B cells and antibodies during Trichuris muris infection using the IgMi mouse
Murphy, E. A.
Fadlullah, Muhammad Z H
Else, K. J.
AffiliationDivision of Infection, Immunity and Respiratory Medicine, Lydia Becker Institute for Immunology, The University of Manchester, Manchester, UK.
MetadataShow full item record
AbstractThe 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. Keywords: B cells; IgMi mouse; Interleukin-10; Intestinal pathology; Th1/Th2; Trichuris muris.
CitationSahputra R, Murphy EA, Forman R, Mair I, Fadlullah MZH, Waisman A, et al. Investigating the importance of B cells and antibodies during Trichuris muris infection using the IgMi mouse. J Mol Med (Berl). 2020;98(9):1301-17.
JournalJournal of Molecular Medicine
- The Essential Role Played by B Cells in Supporting Protective Immunity Against <i>Trichuris muris</i> Infection Is by Controlling the Th1/Th2 Balance in the Mesenteric Lymph Nodes and Depends on Host Genetic Background.
- Authors: Sahputra R, Ruckerl D, Couper KN, Muller W, Else KJ
- Issue date: 2019
- Characterisation of the protective immune response following subcutaneous vaccination of susceptible mice against Trichuris muris.
- Authors: Dixon H, Little MC, Else KJ
- Issue date: 2010 May
- Increased susceptibility to oral Trichuris muris infection in the specific absence of CXCR5<sup>+</sup> CD11c<sup>+</sup> cells.
- Authors: Bradford BM, Donaldson DS, Forman R, Else KJ, Mabbott NA
- Issue date: 2018 Aug
- Distinct DC subsets regulate adaptive Th1 and 2 responses during Trichuris muris infection.
- Authors: Demiri M, Müller-Luda K, Agace WW, Svensson-Frej M
- Issue date: 2017 Oct
- Dendritic cells have a crucial role in the production of cytokines in mesenteric lymph nodes of B10.BR mice infected with Trichuris muris.
- Authors: Koyama K
- Issue date: 2008 Feb