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Gm614 Protects Germinal Center B Cells From Death by Suppressing Caspase-1 Transcription in Lupus-Prone Mice.

ABSTRACT: Only a few signaling pathways have been reported in germinal center (GC) B-cell proliferation and death. In this study, we showed that a novel uncharacterized Gm614 protein is highly expressed in GC B cells from lupus-prone mice. Critically, ablation of this GC B-cell-specific Gm614 promoted GC B-cell death and mitigation of autoimmune symptoms, whereas overexpression protected GC B cells from death and exacerbated autoimmune symptoms. We demonstrated that mechanistically, nuclear-localized Gm614 reduced caspase-1 expression in GC B cells by binding with caspase-1 promoter to suppress its activation. Our results suggest that Gm614 protects GC B cells from death by suppressing caspase-1 transcription in autoimmune diseases. This may provide some hints for targeting the cell proliferation involved in autoimmune diseases.

SUBMITTER: He Y

PROVIDER: S-EPMC7609865 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Gm614 Protects Germinal Center B Cells From Death by Suppressing Caspase-1 Transcription in Lupus-Prone Mice.

He Youdi Y Xu Ruonan R Zhai Bing B Zhou Shan S Wang Xiaoqian X Wang Renxi R

Frontiers in immunology 20201021

Only a few signaling pathways have been reported in germinal center (GC) B-cell proliferation and death. In this study, we showed that a novel uncharacterized Gm614 protein is highly expressed in GC B cells from lupus-prone mice. Critically, ablation of this GC B-cell-specific Gm614 promoted GC B-cell death and mitigation of autoimmune symptoms, whereas overexpression protected GC B cells from death and exacerbated autoimmune symptoms. We demonstrated that mechanistically, nuclear-localized Gm61 ...[more]

PMID: 33193409

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