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The E3 ubiquitin ligase Itch deficiency promotes antigen-driven B-cell responses in mice |
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| Authors: | Ying Fang Youdi He Bing Zhai Chunmei Hou Ruonan Xu Chen Xing Xiaoqian Wang Ning Ma Gencheng Han Renxi Wang |
| Affiliation: | 1. Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China Department of Rheumatology, First Hospital of Jilin University, Changchun, China Fang, He, Zhai, and Hou contributed equally to this work as first authors.;2. Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China Fang, He, Zhai, and Hou contributed equally to this work as first authors.;3. Institute of Military Cognition and Brain Sciences, Beijing, China Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing, China Fang, He, Zhai, and Hou contributed equally to this work as first authors.;4. Institute of Military Cognition and Brain Sciences, Beijing, China Fang, He, Zhai, and Hou contributed equally to this work as first authors.;5. Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China;6. Institute of Military Cognition and Brain Sciences, Beijing, China;7. Staidson (Beijing) Biopharmaceuticals Co., Ltd, Beijing, China;8. Department of Rheumatology, First Hospital of Jilin University, Changchun, China |
| Abstract: | Deficiency of Itch, an E3 ubiquitin ligase, usually induced severe systemic and progressive autoimmune disease. The Itch function is well studied in T cells but not in B cells. We hypothesize that B-cell-specific Itch deficiency promoted antigen-induced B-cell activation and antibody-expressing plasma cell (PC) production. We found that unlike Itch KO, Itch cKO (CD19creItchf/f) mice did not demonstrated a significant increase in the sizes of spleens and LNs, antibody level, and base mutation of antibody gene. However, in line with the fact that Itch expression decreased in GC B cells, PCs, and plasmablast (PB)-like SP 2/0 cells, Itch deficiency promoted B-cell activation and antibody production induced by antigens including lipopolysaccharide (LPS) and sheep red blood cells (SRBCs). Mechanistically, we found that Itch deficiency promotes antigen-induced cytokine production because Itch controls the proteins (e.g., eIF3a, eIF3c, eIF3h) with translation initiation factor activity. Altogether, our data suggest that Itch deficiency promotes antigen-driven B-cell response. This may provide hints for Itch-targeted treatment of patients with autoimmune disease. |
| Keywords: | antigen B cells GC B cells itch plasma cells |