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Investigating the importance of B cells and antibodies during Trichuris muris infection using the IgMi mouse
Sahputra, R. Murphy, E. A. Forman, R. Mair, I. Fadlullah, Muhammad Z H Waisman, A. Muller, W. Else, K. J.
Sahputra, R.
Murphy, E. A.
Forman, R.
Mair, I.
Fadlullah, Muhammad Z H
Waisman, A.
Muller, W.
Else, K. J.
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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.
Keywords: B cells; IgMi mouse; Interleukin-10; Intestinal pathology; Th1/Th2; Trichuris muris.
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Date
2020
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Sahputra 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.