SUMO-specific protease 1 regulates germinal center B cell response through deSUMOylation of PAX5.
Proc Natl Acad Sci U S A
; 121(22): e2314619121, 2024 May 28.
Article
em En
| MEDLINE
| ID: mdl-38776375
ABSTRACT
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Cisteína Endopeptidases
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Linfócitos B
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Centro Germinativo
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Fator de Transcrição PAX5
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Sumoilação
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article