浙江大学学报（医学版）2026，Vol.55Issue(4)：321-331,11.DOI:10.3724/zdxbyxb-2025-0646
B细胞内源性拟素化可调控小鼠免疫反应
Endogenous neddylation in B cells regulates immune responses in mice
摘要
Abstract
Objective:To investigate the regulatory role of endogenous neddylation in B cell-mediated immune responses.Methods:B cell-specific Ube2m knockout mice(CD19cre/+Ube2mfl/fl)were generated using the Cre-LoxP system,with littermate Ube2mfl/fl mice serving as normal controls.Mice were immunized with thymus-independent antigens 4-hydroxy-3-nitrophenylacetyl(NP)-lipopoly saccharide(LPS)and 2,4-dinitrophenyl(DNP)-Ficoll,as well as thymus-dependent antigens NP-chicken gamma globulin(CGG)and DNP-keyhole limpet hemocyanin(KLH).Serum levels of specific antibodies were measured by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was used to determine the proportions of splenic germinal center B cells,splenic plasma cells,and bone marrow plasma cells in mice immunized with NP-LPS or NP-CGG.Statistical analyses were performed to assess differences in immune responses among the groups.Results:Compared with controls,Ube2m-deficient mice showed significantly lower levels of anti-NP immunoglobulin(Ig)G2a,IgG2b,IgG2c,and IgG3 after NP-LPS immunization,and reduced levels of all anti-DNP IgG subclasses after DNP-Ficoll immunization(all P<0.05),with no significant change in IgM levels.The proportions of total splenic germinal center B cells,total bone marrow plasma cells,and NP-specific plasma cells were also significantly decreased after NP-LPS immunization(all P<0.01).Following immunization with NP-CGG or DNP-KLH,Ube2m knockout mice exhibited reduced levels of anti-NP or anti-DNP IgM and all IgG subclasses(all P<0.05),with antigen-dependent differences in the timing and extent of antibody reduction.After NP-CGG immunization,the proportions of total splenic plasma cells,NP-specific plasma cells,and NP-specific germinal center B cells were markedly decreased(all P<0.01).Conclusion:Endogenous neddylation deficiency in B cells broadly impairs immune responses to both thymus-independent and thymus-dependent antigens in mice,and its regulatory effects are antigen-dependent.关键词
拟素化/Ube2m/B淋巴细胞/胸腺依赖性抗原/非胸腺依赖性抗原/小鼠Key words
Neddylation/Ube2m/B lymphocyte/Thymus dependent antigen/Thymus independent antigen/Mice分类
医药卫生引用本文复制引用
金鑫,竺露瑶,章力之,陈天杭,周明倩..B细胞内源性拟素化可调控小鼠免疫反应[J].浙江大学学报（医学版）,2026,55(4):321-331,11.基金项目
浙江省自然科学基金(LQ23H270005) （LQ23H270005）
浙江中医药大学校级科研项目(2021RCZXZK12) （2021RCZXZK12）
浙江中医药大学研究生科学研究基金(2024YKJ13)This study was supported by Zhejiang Provincial Natural Science Foundation of China(LQ23H270005),Scientific Research Project of Zhejiang Chinese Medical University(2021RCZXZK12),and Graduate Research Fund of Zhejiang Chinese Medical University(2024YKJ13) （2024YKJ13）
