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

• Published in: Journal of molecular medicine (Berlin, Germany) Germany), 2020-09, Vol.98 (9), p.1301-1317
• Main Authors: Sahputra, Rinal, Murphy, Emma A, Forman, Ruth, Mair, Iris, Fadlullah, Muhammad Z. H., Waisman, Ari, Muller, Werner, Else, Kathryn J.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies - immunology; Apoptosis; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Biomedical and Life Sciences; Biomedicine; Chronic infection; Class switching; Cytokines - biosynthesis; Digestive system; Disease Models, Animal; Disease Susceptibility - immunology; Female; Gastrointestinal tract; Helper cells; Homeostasis; Host-Parasite Interactions - immunology; Human Genetics; Immunoglobulin M; Immunoregulation; Infections; Interleukin 10; Internal Medicine; Intestine; Lymph nodes; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Lymphocytes B; Lymphocytes T; Male; Mice; Mice, Knockout; Molecular Medicine; Original; Original Article; Parasite Load; Phenotypes; Ribonucleic acid; RNA; Trichuriasis - immunology; Trichuriasis - parasitology; Trichuris - immunology; Trichuris muris
• ISSN: 0946-2716; 1432-1440
• DOI: 10.1007/s00109-020-01954-3

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.