StarD5 modulates B cell cholesterol synthesis and IgG1 plasma cell differentiation

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 ...

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Main Authors: Anuj Tharakan, Daniel Rodriguez-Agudo, Sheela Damle, Genta Kakiyama, William M. Pandak, Gregorio Gil, Rebecca K. Martin
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Biochemistry and Biophysics Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2405580824002371
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author Anuj Tharakan
Daniel Rodriguez-Agudo
Sheela Damle
Genta Kakiyama
William M. Pandak
Gregorio Gil
Rebecca K. Martin
author_facet Anuj Tharakan
Daniel Rodriguez-Agudo
Sheela Damle
Genta Kakiyama
William M. Pandak
Gregorio Gil
Rebecca K. Martin
author_sort Anuj Tharakan
collection DOAJ
description 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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spelling doaj-art-425909eb7685452699ca098fa65a991c2025-08-20T02:30:32ZengElsevierBiochemistry and Biophysics Reports2405-58082024-12-014010187310.1016/j.bbrep.2024.101873StarD5 modulates B cell cholesterol synthesis and IgG1 plasma cell differentiationAnuj Tharakan0Daniel Rodriguez-Agudo1Sheela Damle2Genta Kakiyama3William M. Pandak4Gregorio Gil5Rebecca K. Martin6Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USADepartment of Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA; Central Virginia VA Healthcare System, Richmond, VA, 23248, USADepartment of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USADepartment of Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA; Central Virginia VA Healthcare System, Richmond, VA, 23248, USADepartment of Medicine, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA; Central Virginia VA Healthcare System, Richmond, VA, 23248, USA; Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USADepartment of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA; Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USADepartment of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA; Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USA; Corresponding author. Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, VA, 23298, USAStarD5 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.http://www.sciencedirect.com/science/article/pii/S2405580824002371
spellingShingle Anuj Tharakan
Daniel Rodriguez-Agudo
Sheela Damle
Genta Kakiyama
William M. Pandak
Gregorio Gil
Rebecca K. Martin
StarD5 modulates B cell cholesterol synthesis and IgG1 plasma cell differentiation
Biochemistry and Biophysics Reports
title StarD5 modulates B cell cholesterol synthesis and IgG1 plasma cell differentiation
title_full StarD5 modulates B cell cholesterol synthesis and IgG1 plasma cell differentiation
title_fullStr StarD5 modulates B cell cholesterol synthesis and IgG1 plasma cell differentiation
title_full_unstemmed StarD5 modulates B cell cholesterol synthesis and IgG1 plasma cell differentiation
title_short StarD5 modulates B cell cholesterol synthesis and IgG1 plasma cell differentiation
title_sort stard5 modulates b cell cholesterol synthesis and igg1 plasma cell differentiation
url http://www.sciencedirect.com/science/article/pii/S2405580824002371
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