 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jul 13, 2024 |
| Title |
B cell-intrinsic IFN-g promotes CD11c+ age-associated B cell differentiation and compromises affinity-based germinal center selection in lupus |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Lupus patients respond less efficiently to vaccinations and are more susceptible to infections. Previously, we have shown, in lupus models, that excessive CD11c+ age-associated B cells (ABCs) not only contribute to autoantibody production but also compromise antigen-specific germinal center (GC) B cell selection and affinity maturation by promoting aberrant T cell activation. Yet, how CD11c+ ABC differentiation is regulated is not fully understood. Here we show that B cell-intrinsic IFN-γ is required for excessive CD11c+ ABC differentiation in lupus mice. B cell-intrinsic IFN-γ is mainly produced by CD11c+ ABCs. IFN-γ-deficiency leads to decreased expression of ABC characteristic genes, including Zeb2, an ABC-specific transcription factor recently described. We further show that ablating IFN-γ can normalize T cell overactivation and rescue antigen-specific GC responses in lupus mice. Our study offers insight into the crucial role of B cell-intrinsic IFN-γ in promoting CD11c+ ABC differentiation and compromising affinity-based germinal center selection and affinity maturation in lupus, providing a potential target for lupus treatment.
|
| |
|
| Overall design |
To understand the impact of B cell-intrinsic IFN-g on CD11c+ ABC differentiation, we sorted CD11c+ ABCs from spleens of ShipDBIfng-/- and ShipDB mice. Following total RNA extraction, we employed SMART-seq for comprehensive transcriptomic profiling.
|
| |
|
| Contributor(s) |
Liu S, Zhang W, Tian S, Zhang Y, Yin Z, Huang G, Zhang H, Li F |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Jul 08, 2024 |
| Last update date |
Jul 13, 2024 |
| Contact name |
Fubin Li |
| E-mail(s) |
fubin.li@sjtu.edu.cn
|
| Phone |
18918925314
|
| Organization name |
Shanghai Jiao Tong University School of Medicine
|
| Street address |
280 South Chongqing Road, Shanghai, 200025, China
|
| City |
Shanghai |
| State/province |
Shanghai |
| ZIP/Postal code |
200025 |
| Country |
China |
| |
|
| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (1) |
|
| Relations |
| BioProject |
PRJNA1132944 |
|
|
|
|
 |
