CRISPR/Cas9 editing reveals IRF8 regulated gene signatures restraining plasmablast differentiation
The transcription factor Interferon regulatory factor 8 (IRF8) is involved in maintaining B cell identity. However, how IRF8 regulates T cell independent B cell responses are not fully characterized. Here, an in vivo CRISPR/Cas9 system was optimized to generate Irf8-deficient murine B cells and used...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-06-01
|
| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023047357 |
| _version_ | 1797796424804466688 |
|---|---|
| author | Zhihong Zuo Anna K. Kania Dillon G. Patterson Sakeenah L. Hicks Jeffrey Maurer Mansi Gupta Jeremy M. Boss Christopher D. Scharer |
| author_facet | Zhihong Zuo Anna K. Kania Dillon G. Patterson Sakeenah L. Hicks Jeffrey Maurer Mansi Gupta Jeremy M. Boss Christopher D. Scharer |
| author_sort | Zhihong Zuo |
| collection | DOAJ |
| description | The transcription factor Interferon regulatory factor 8 (IRF8) is involved in maintaining B cell identity. However, how IRF8 regulates T cell independent B cell responses are not fully characterized. Here, an in vivo CRISPR/Cas9 system was optimized to generate Irf8-deficient murine B cells and used to determine the role of IRF8 in B cells responding to LPS stimulation. Irf8-deficient B cells more readily formed CD138+ plasmablasts in response to LPS with the principal dysregulation occurring at the activated B cell stage. Transcriptional profiling revealed an upregulation of plasma cell associated genes prematurely in activated B cells and a failure to repress the gene expression programs of IRF1 and IRF7 in Irf8-deficient cells. These data expand on the known roles of IRF8 in regulating B cell identity by preventing premature plasma cell formation and highlight how IRF8 helps evolve TLR responses away from the initial activation towards those driving humoral immunity. |
| first_indexed | 2024-03-13T03:32:53Z |
| format | Article |
| id | doaj.art-e2d535e0932a4c759017e58be7c52fae |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-13T03:32:53Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-e2d535e0932a4c759017e58be7c52fae2023-06-24T05:18:11ZengElsevierHeliyon2405-84402023-06-0196e17527CRISPR/Cas9 editing reveals IRF8 regulated gene signatures restraining plasmablast differentiationZhihong Zuo0Anna K. Kania1Dillon G. Patterson2Sakeenah L. Hicks3Jeffrey Maurer4Mansi Gupta5Jeremy M. Boss6Christopher D. Scharer7Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA 30322, USA; Current Address: Xiangya Hospital, Central South University, Changsha, 410008, ChinaDepartment of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA 30322, USADepartment of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA 30322, USADepartment of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA 30322, USADepartment of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA 30322, USADepartment of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA 30322, USADepartment of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA 30322, USADepartment of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA 30322, USA; Corresponding author.The transcription factor Interferon regulatory factor 8 (IRF8) is involved in maintaining B cell identity. However, how IRF8 regulates T cell independent B cell responses are not fully characterized. Here, an in vivo CRISPR/Cas9 system was optimized to generate Irf8-deficient murine B cells and used to determine the role of IRF8 in B cells responding to LPS stimulation. Irf8-deficient B cells more readily formed CD138+ plasmablasts in response to LPS with the principal dysregulation occurring at the activated B cell stage. Transcriptional profiling revealed an upregulation of plasma cell associated genes prematurely in activated B cells and a failure to repress the gene expression programs of IRF1 and IRF7 in Irf8-deficient cells. These data expand on the known roles of IRF8 in regulating B cell identity by preventing premature plasma cell formation and highlight how IRF8 helps evolve TLR responses away from the initial activation towards those driving humoral immunity.http://www.sciencedirect.com/science/article/pii/S2405844023047357CRISPR/Cas9Cas9 ribonucleoproteinGene editingHematopoietic stem cellsPrimary mouse B cellsIRF8 |
| spellingShingle | Zhihong Zuo Anna K. Kania Dillon G. Patterson Sakeenah L. Hicks Jeffrey Maurer Mansi Gupta Jeremy M. Boss Christopher D. Scharer CRISPR/Cas9 editing reveals IRF8 regulated gene signatures restraining plasmablast differentiation Heliyon CRISPR/Cas9 Cas9 ribonucleoprotein Gene editing Hematopoietic stem cells Primary mouse B cells IRF8 |
| title | CRISPR/Cas9 editing reveals IRF8 regulated gene signatures restraining plasmablast differentiation |
| title_full | CRISPR/Cas9 editing reveals IRF8 regulated gene signatures restraining plasmablast differentiation |
| title_fullStr | CRISPR/Cas9 editing reveals IRF8 regulated gene signatures restraining plasmablast differentiation |
| title_full_unstemmed | CRISPR/Cas9 editing reveals IRF8 regulated gene signatures restraining plasmablast differentiation |
| title_short | CRISPR/Cas9 editing reveals IRF8 regulated gene signatures restraining plasmablast differentiation |
| title_sort | crispr cas9 editing reveals irf8 regulated gene signatures restraining plasmablast differentiation |
| topic | CRISPR/Cas9 Cas9 ribonucleoprotein Gene editing Hematopoietic stem cells Primary mouse B cells IRF8 |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023047357 |
| work_keys_str_mv | AT zhihongzuo crisprcas9editingrevealsirf8regulatedgenesignaturesrestrainingplasmablastdifferentiation AT annakkania crisprcas9editingrevealsirf8regulatedgenesignaturesrestrainingplasmablastdifferentiation AT dillongpatterson crisprcas9editingrevealsirf8regulatedgenesignaturesrestrainingplasmablastdifferentiation AT sakeenahlhicks crisprcas9editingrevealsirf8regulatedgenesignaturesrestrainingplasmablastdifferentiation AT jeffreymaurer crisprcas9editingrevealsirf8regulatedgenesignaturesrestrainingplasmablastdifferentiation AT mansigupta crisprcas9editingrevealsirf8regulatedgenesignaturesrestrainingplasmablastdifferentiation AT jeremymboss crisprcas9editingrevealsirf8regulatedgenesignaturesrestrainingplasmablastdifferentiation AT christopherdscharer crisprcas9editingrevealsirf8regulatedgenesignaturesrestrainingplasmablastdifferentiation |