SUMO- specific protease 1 regulates germinal center B cell response through deSUMOylation of PAX5

• 成果类型: Article
• 署名作者: Qi, Jingjing; Yan, Lichong; Sun, Jiping; Huang, Chuanxin; Su, Bing; Cheng, Jinke; Shen, Lei
• 署名单位: Chinese Academy of Sciences; Shanghai Jiao Tong University; Shanghai Jiao Tong University; Shanghai Jiao Tong University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8859
• DOI: 10.1073/pnas.2314619121
• 发表日期: 2024-05-28
• 关键词: cytidine deaminase aid; mechanisms; receptor; hypermutation; sumoylation; homeostasis; expression

摘要

Humoral immunity depends on the germinal center (GC) reaction where B cells are tightly controlled for class - switch recombination and somatic hypermutation and finally generated into plasma and memory B cells. However, how protein SUMOylation regulates the process of the GC reaction remains largely unknown. Here, we show that the expression of SUMO - specific protease 1 (SENP1) is up - regulated in GC B cells. Selective ablation of SENP1 in GC B cells results in impaired GC dark and light zone organization and reduced IgG1 - switched GC B cells, leading to diminished production of class - switched antibodies with high - affinity in response to a TD antigen challenge. Mechanistically, SENP1 directly binds to Paired box protein 5 (PAX5) to mediate PAX5 deSUMOylation, sustaining PAX5 protein stability to promote the transcription of activation - induced cytidine deaminase. In summary, our study uncovers SUMOylation as an important posttranslational mechanism regulating GC B cell response.