Tharakan Anuj, Rodriguez-Agudo Daniel, Damle Sheela, Kakiyama Genta, Pandak William M, Gil Gregorio, Martin Rebecca K
Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA.
Department of Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA.
Biochem Biophys Rep. 2024 Nov 15;40:101873. doi: 10.1016/j.bbrep.2024.101873. eCollection 2024 Dec.
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.
StarD5是一种内质网应激蛋白，它能结合胆固醇并将其转运至质膜。它还能结合并调节25-羟基胆固醇（25-HC）的水平。然而，StarD5-25-HC轴的完整功能尚不清楚。最近有研究表明，25-HC是派尔集合淋巴结中IgA+浆细胞分化的重要抑制因子，并调节生发中心与浆细胞之间的转换。由于StarD5能调节25-HC，我们利用StarD5基因敲除小鼠研究了StarD5在B细胞中的作用。我们发现，StarD5基因敲除小鼠在基线时B细胞发育和抗体产生正常，但在依赖T细胞的免疫接种后，观察到类别转换的IgG1生发中心B细胞和浆细胞减少。非依赖T细胞的免疫反应还会导致IgG1反应减少，这可能是B细胞内在的原因。此外，在非依赖T细胞的免疫接种后，T1至T2过渡性B细胞阶段出现了损伤。总之，StarD5似乎对B细胞中IgG1反应很重要，并且可能在应激条件下调节B细胞发育。我们的研究结果表明，StarD5在免疫接种后作为B细胞功能和激活的关键调节因子发挥作用。
