title: Epithelial cells are a source of natural IgM that contribute to innate immune responses.
abstract: Currently, natural IgM antibodies are considered to be the constitutively secreted products of B-1 cells in mice and humans. In this study, we found that mouse epithelial cells, including liver epithelial cells and small intestinal epithelial cells (IECs), could express IgM that also showed natural antibody activity. Moreover, similar to the B-1 cell-derived natural IgM that can be upregulated by TLR9 agonists (mimicking bacterial infection), the expression of epithelial cell-derived natural IgM could also be significantly increased by TLR9 signaling. More importantly, the epithelial cell-derived IgM was polyreactive, and it could recognize single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), lipopolysaccharide (LPS), and insulin with low affinity; additionally, TLR9 agonists could enhance it in a MyD88-dependent manner. Furthermore, epithelial cell-derived IgM could bind various bacteria; therefore, it could be involved in anti-infection responses. Together, these results highlight the fact that epithelial cells are an important source of natural IgM, in addition to that produced by B-1 cells, and IgM contributes to the innate immune responses in local tissues, further demonstrating that the epithelium is a first line of defense in the protection against invading microbes.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Shao
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China.
authors.forename: Fanlei
authors.initials: F
authors.lastname: Hu
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Beijing 100191, China.
authors.forename: Junfan
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Qinyuan
authors.initials: Q
authors.lastname: Liao
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Medical Immunology, Ministry of Health, Beijing 100191, China.
authors.forename: Enyang
authors.initials: E
authors.lastname: Liu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China; Key Laboratory of Medical Immunology, Ministry of Health, Beijing 100191, China. Electronic address: qiuxy@bjmu.edu.cn.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Qiu
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D001419:Bacteria / Q000276:immunology; D002478:Cells, Cultured; D004277:DNA, Single-Stranded / Q000276:immunology; D004847:Epithelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D007113:Immunity, Innate / Q000502:physiology*; D007075:Immunoglobulin M / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D015398:Signal Transduction / Q000502:physiology; D051217:Toll-Like Receptor 9 / Q000037:antagonists & inhibitors
chemical_list: D004277:DNA, Single-Stranded; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D051217:Toll-Like Receptor 9
keywords: Epithelial cells; Innate immune response; Natural IgM; TLR9 agonists