PMID- 32387557 OWN - NLM STAT- MEDLINE DCOM- 20210915 LR - 20210915 IS - 1879-0089 (Electronic) IS - 0145-305X (Linking) VI - 110 DP - 2020 Sep TI - Splicing variants of grass carp (Ctenopharyngodon idellus) IL-21: Functions in IgM(+) B cell proliferation and IgM secretion. PG - 103728 LID - S0145-305X(20)30007-0 [pii] LID - 10.1016/j.dci.2020.103728 [doi] AB - In mammals, interleukin 21 (IL-21) is a type I four-helical bundle cytokine produced by activated T cells that has pleiotropic functions on immune cells. Although IL-21 has been discovered in fish, the splicing variants of this cytokine and their functions on B cells are unclear. In this study, based on the original transcript of grass carp IL-21 (named gcIL-21sv1 in this study), two alternative splicing variants, named gcIL-21sv2 and gcIL-21sv3, were cloned and characterized. The protein sequences of gcIL-21sv1 and gcIL-21sv2 consist of four alpha-helixes, and only the six amino acid residues at the C-terminal are different. Unlike gcIL-21sv1 and gcIL-21sv2, gcIL-21sv3 lacks the C-terminal region. The expression analysis showed that gcIL-21sv1, gcIL-21sv2, and gcIL-21sv3 were constitutively expressed in all the tested tissues, and their expression could be significantly up-regulated by LPS and Poly (I:C) in head kidney leukocytes (HKLs), with the fold change of gcIL-21sv1 being higher than that of gcIL-21sv2 and gcIL-21sv3. Recombinant gcIL-21sv1 and gcIL-21sv2, but not gcIL-21sv3, could induce the proliferation of IgM(+) B cells and the secretion of IgM, with the activity of gcIL-21sv1 being stronger than that of gcIL-21sv2, indicating that the C-terminal region plays important roles in the function of gcIL-21. Taken together, this study found that, like IL-21 in human and mouse, IL-21 splicing variants also exist in fish, and the regulatory activities of these variants in humoral immunity are differ, suggesting that grass carp may balance the immune response mediated by IL-21 through alternative splicing. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Cui, Zheng-Wei AU - Cui ZW AD - Key Laboratory of Fishery Drug Development, Ministry of Agriculture, Key Laboratory of Aquatic Animal Immune Technology, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510380, China. FAU - Zhang, Xiang-Yang AU - Zhang XY AD - Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, Fujian Agriculture and Forestry University, Fuzhou, 350002, China. FAU - Chen, Xiao-Hua AU - Chen XH AD - Department of Clinical Laboratory, General Hospital of Central Theater Command, PLA, Wuhan, 430070, China. Electronic address: cxhniuniu@163.com. FAU - Zhang, Xu-Jie AU - Zhang XJ AD - State Key Laboratory of Agricultural Microbiology, College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China. Electronic address: xujiezhang@mail.hzau.edu.cn. FAU - Zhang, Yong-An AU - Zhang YA AD - State Key Laboratory of Agricultural Microbiology, College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China; Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266071, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200506 PL - United States TA - Dev Comp Immunol JT - Developmental and comparative immunology JID - 7708205 RN - 0 (Fish Proteins) RN - 0 (Immunoglobulin M) RN - 0 (Interleukins) RN - 0 (Lipopolysaccharides) RN - MKM3CA6LT1 (interleukin-21) RN - O84C90HH2L (Poly I-C) SB - IM MH - Alternative Splicing MH - Animals MH - B-Lymphocytes/*immunology MH - Carps/*immunology MH - Cell Proliferation MH - Cloning, Molecular MH - Fish Proteins/genetics/*metabolism MH - Head Kidney/*immunology MH - Humans MH - Immunity, Humoral MH - Immunoglobulin M/*metabolism MH - Interleukins/genetics/*metabolism MH - Leukocytes/*immunology MH - Lipopolysaccharides/immunology MH - Lymphocyte Activation MH - Mice MH - Poly I-C/immunology OTO - NOTNLM OT - B cell OT - Grass carp OT - IL-21 OT - IgM OT - Splicing variant EDAT- 2020/05/11 06:00 MHDA- 2021/09/16 06:00 CRDT- 2020/05/11 06:00 PHST- 2020/01/07 00:00 [received] PHST- 2020/03/03 00:00 [revised] PHST- 2020/04/29 00:00 [accepted] PHST- 2020/05/11 06:00 [pubmed] PHST- 2021/09/16 06:00 [medline] PHST- 2020/05/11 06:00 [entrez] AID - S0145-305X(20)30007-0 [pii] AID - 10.1016/j.dci.2020.103728 [doi] PST - ppublish SO - Dev Comp Immunol. 2020 Sep;110:103728. doi: 10.1016/j.dci.2020.103728. Epub 2020 May 6.