StarD5 modulates B cell cholesterol synthesis and IgG1 plasma cell differentiation

IF 2.3 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports Pub Date : 2024-11-15 DOI:10.1016/j.bbrep.2024.101873

Anuj Tharakan , Daniel Rodriguez-Agudo , Sheela Damle , Genta Kakiyama , William M. Pandak , Gregorio Gil , Rebecca K. Martin

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引用次数: 0

Abstract

StarD5 is an ER stress protein that binds cholesterol and transfers it to the plasma membrane. It additionally binds and regulates 25-hydroxycholesterol (25-HC) levels. However the full function of the StarD5-25-HC axis is unknown. 25-HC has been recently described as an important suppressor of IgA + plasma cell differentiation in the Peyer's patches, and regulates the switch between germinal center and plasma cells. Since StarD5 regulates 25-HC, we examined the role of StarD5 in B cells using StarD5^−/− mice. We found that StarD5^−/− mice have normal B cell development and antibody production at baseline, but after T-dependent immunization a reduction in class-switched IgG1 germinal center B cells and plasma cells was observed. T-independent immune responses additionally result in a reduction in IgG1 responses and this likely B cell intrinsic. In addition, there was impairment at the T1 to T2 transitional B cell stage after T-independent immunization. In conclusion, StarD5 appears important for IgG1 responses in B cells and may regulate B cell development under stress conditions. Our findings suggest a role for StarD5 as a key regulator of B cell function and activation following immunization.

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StarD5 调节 B 细胞胆固醇合成和 IgG1 浆细胞分化

StarD5 是一种ER应激蛋白，能结合胆固醇并将其转移到质膜上。此外，它还能结合并调节 25-羟基胆固醇（25-HC）的水平。然而，StarD5-25-HC 轴的全部功能尚不清楚。最近，25-HC 被描述为佩尔斑块中 IgA + 浆细胞分化的重要抑制因子，并调节生殖中心和浆细胞之间的转换。由于 StarD5 可调控 25-HC，我们利用 StarD5-/- 小鼠研究了 StarD5 在 B 细胞中的作用。我们发现，StarD5-/-小鼠的 B 细胞发育和抗体产生在基线时正常，但在 T 依赖性免疫后，类开关 IgG1 生发中心 B 细胞和浆细胞减少。T 依赖性免疫反应也会导致 IgG1 反应的减少，这可能是 B 细胞内在的原因。此外，在 T 依赖性免疫后，T1 到 T2 过渡 B 细胞阶段也出现了损伤。总之，StarD5 似乎对 B 细胞的 IgG1 反应很重要，并可能在应激条件下调节 B 细胞的发育。我们的研究结果表明，StarD5 是免疫后 B 细胞功能和活化的关键调节因子。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics

CiteScore

4.60

自引率

0.00%

发文量

191

审稿时长

59 days

期刊介绍： Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.