Defective immune responses in mice lacking LUBAC‐mediated linear ubiquitination in B cells |
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| Authors: | Yoshiteru Sasaki Soichi Sano Masaki Nakahara Shigeo Murata Kohei Kometani Yuichi Aiba Shinji Sakamoto Yoshihiro Watanabe Keiji Tanaka Tomohiro Kurosaki Kazuhiro Iwai |
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| Institution: | 1. Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, , Kyoto, Japan;2. Department of Biophysics and Biochemistry, Graduate School of Medicine, Osaka University, , Suita, Japan;3. Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, University of Tokyo, , Tokyo, Japan;4. Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, , Yokohama, Japan;5. Pharmaceutical Frontier Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., , Yokohama, Japan;6. Laboratory of Frontier Science, Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science, , Tokyo, Japan;7. Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, , Suita, Japan |
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| Abstract: | The linear ubiquitin chain assembly complex (LUBAC) plays a crucial role in activating the canonical NF‐κB pathway, which is important for B‐cell development and function. Here, we describe a mouse model (B‐HOIPΔlinear) in which the linear polyubiquitination activity of LUBAC is specifically ablated in B cells. Canonical NF‐κB and ERK activation, mediated by the tumour necrosis factor (TNF) receptor superfamily receptors CD40 and TACI, was impaired in B cells from B‐HOIPΔlinear mice due to defective activation of the IKK complex; however, B‐cell receptor (BCR)‐mediated activation of the NF‐κB and ERK pathways was unaffected. B‐HOIPΔlinear mice show impaired B1‐cell development and defective antibody responses to thymus‐dependent and thymus‐independent II antigens. Taken together, these data suggest that LUBAC‐mediated linear polyubiquitination is essential for B‐cell development and activation, possibly via canonical NF‐κB and ERK activation induced by the TNF receptor superfamily, but not by the BCR. |
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| Keywords: | antibody response B cell canonical NF‐κ B pathway ERK linear ubiquitin chain assembly complex |
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