Evaluating the IgMi mouse as a novel tool to study B‐cell biology

Sahputra, Rinal; Yam‐Puc, Juan Carlos; Waisman, Ari; Müller, Werner; Else, Kathryn J.

doi:10.1002/eji.201847735

Cited by 10 publications

(16 citation statements)

References 10 publications

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“…This study therefore investigated the role of B cells and antibodies in immunity to T. muris infection using α-CD20 mAb to deplete B cells from C57BL/6 and BALB/c mice. Adopting an α-CD20 mAb-mediated B cell approach allows for the depletion of CD19+ cells either prior to or post infection Further, it avoids the complicating consequences of B cell deficiency during embryonic development (21,22). We demonstrate that B cells are important in the development and maintenance of the protective immune response to T. muris.…”

Section: Introductionmentioning

confidence: 90%

“…All protocols to maintain the parasite were as previously described (21)(22)(23)(24). The parasite was passaged through SCID mice that are susceptible to T. muris infection.…”

Section: Maintenance Of Parasite and Preparation Of Egg Batchesmentioning

confidence: 99%

“…During necropsy, the cecum and proximal colon were collected and stored at −20 • C before analysis (22). Before worm count, the intestine was thawed at room temperature and cut longitudinally using blunt-ended scissors and the epithelium was scraped using curved forceps in a petri dish.…”

Section: Quantification Of T Muris Wormsmentioning

confidence: 99%

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The Essential Role Played by B Cells in Supporting Protective Immunity Against Trichuris muris Infection Is by Controlling the Th1/Th2 Balance in the Mesenteric Lymph Nodes and Depends on Host Genetic Background

et al. 2019

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How B cells contribute to protective immunity against parasitic nematodes remains unclear, with their importance as accessory cells underexplored. In this study, anti-CD20 monoclonal antibody (α-CD20 mAb)-mediated depletion of B cells from C57BL/6 mice revealed an important role for B cells in supporting Th2 immune responses and thus expulsion of Trichuris muris (T. muris). C57BL/6 mice normally mount mixed Th1/Th2 immune responses to T. muris and expel the parasite by the third week post infection. However, B cell-depleted C57BL/6 had significantly reduced Th2-type cytokines post infection and failed to expel the parasite. IFN-γ production in the MLN of C57BL/6 mice receiving α-CD20 mAb treatment was not affected, collectively resulting in an overall change in Th1/Th2 balance in favor of Th1. Further, the expression of IFN-γ and IFN-γinduced genes at the effector site, the gut, was significantly increased in the absence of B cells. Interestingly, and in complete contrast, BALB/c mice, which mount strongly polarized Th2 immune responses, rather than mixed Th1/Th2 immune responses, were still able to expel T. muris in the absence of B cells. We thus hypothesized that the B cell plays a critical role in enabling strong Th2 responses in the context of mixed Th1/Th2 settings, with the role becoming redundant in highly Th2 polarized environments. In support of this, neutralization of IFN-γ in B cell depleted C57BL/6 restored resistance against T. muris infection. Thus, our data suggest an important role of B cells in supporting Th2-type immune responses in mixed IFN-γ-rich Th1/Th2 settings.

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Section: Introductionmentioning

confidence: 90%

“…All protocols to maintain the parasite were as previously described (21)(22)(23)(24). The parasite was passaged through SCID mice that are susceptible to T. muris infection.…”

Section: Maintenance Of Parasite and Preparation Of Egg Batchesmentioning

confidence: 99%

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The Essential Role Played by B Cells in Supporting Protective Immunity Against Trichuris muris Infection Is by Controlling the Th1/Th2 Balance in the Mesenteric Lymph Nodes and Depends on Host Genetic Background

et al. 2019

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“…The IgMi mouse was first introduced as IgH μγ1/μγ1 [ 10 ] before it subsequently became known as the IgMi mouse [ 11 ]. In our previous study, we have characterised the IgMi mouse on a C57BL/6 genetic background at steady state [ 12 ]. Although the IgMi mouse has normal B cell development, and expresses surface IgM, this mouse is unable to secrete any soluble antibodies [ 10 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…In our previous study, we have characterised the IgMi mouse on a C57BL/6 genetic background at steady state [ 12 ]. Although the IgMi mouse has normal B cell development, and expresses surface IgM, this mouse is unable to secrete any soluble antibodies [ 10 , 12 ]. Thus, the IgMi mouse offers a model system enabling the discrimination between antibody dependent and antibody independent B cell functions.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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The B side of B cells in NAFLD

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2022

Hepatology

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Evaluating the IgMi mouse as a novel tool to study B‐cell biology

Cited by 10 publications

References 10 publications

The Essential Role Played by B Cells in Supporting Protective Immunity Against Trichuris muris Infection Is by Controlling the Th1/Th2 Balance in the Mesenteric Lymph Nodes and Depends on Host Genetic Background

The Essential Role Played by B Cells in Supporting Protective Immunity Against Trichuris muris Infection Is by Controlling the Th1/Th2 Balance in the Mesenteric Lymph Nodes and Depends on Host Genetic Background

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

The B side of B cells in NAFLD

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