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| Status |
Public on Sep 17, 2024 |
| Title |
Bank1 modulates the differentiation and molecular profile of key B cell populations in autoimmunity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
This study aimed at defining the role of the B-cell adaptor protein BANK1 in the appearance of age-associated B cells (ABCs) in two SLE mouse models (TLR7.tg6 and Imiquimod-induced mice), crossed with Bank1-/- mice. The absence of Bank1 led to a significant reduction in ABC levels, also affecting other B cell populations. To gain deeper insights into their differentiation pathway and the impact of Bank1 on B cell populations, a single-cell transcriptome assay was performed. In the TLR7.tg6 model, we identified 10 clusters within B cells, including an ABC-specific cluster which was decreased in Bank1-deficient mice. In its absence, ABCs exhibited an anti-inflammatory gene expression profile, while being pro-inflammatory in Bank1-sufficient lupus mice. Trajectory analyses revealed that ABCs originated from marginal zone and memory-like B cells, ultimately acquiring transcriptional characteristics associated with atypical memory cells and long-lived plasma cells. Also, Bank1 deficiency normalized the presence of naïve B cells, which were nearly absent in lupus mice. Interestingly, Bank1 deficiency significantly reduced a distinct cluster containing IFN-responsive genes. These findings underscore the critical role of Bank1 in ABC development, impacting early B cell stages towards ABC differentiation, and the presence of IFN-stimulated gene-containing B cells, both populations determinant for autoimmunity.
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| Overall design |
Transcriptomic data were obtained from single cells sorted from total splenocytes of three mice per group: healthy control wild-type, TLR7.tg6 and TLR7.tg6.Bank1-/- mice
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| Web link |
https://insight.jci.org/articles/view/179417
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| |
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| Contributor(s) |
Gómez Hernández G, Toro Domínguez D, Galicia G, Morell M, Alarcón Riquelme ME |
| Citation(s) |
39163122 |
| |
| Submission date |
Jul 08, 2024 |
| Last update date |
Sep 18, 2024 |
| Contact name |
Daniel Toro |
| E-mail(s) |
danieltorodominguez@gmail.com
|
| Organization name |
GENYO
|
| Department |
Bioinformatics
|
| Street address |
Avenida de la Ilustracion
|
| City |
GRANADA |
| State/province |
Spain |
| ZIP/Postal code |
18016 |
| Country |
Spain |
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| Platforms (1) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA1132938 |
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