|
| Status |
Public on Mar 22, 2021 |
| Title |
Transcriptional profiling of mouse germinal center B cells (B220+, GL7+, CD95+) isolated from GC-specific (Cg1-Cre) DAF-TM transgenic or control mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Germinal centers (GCs) support diversification and affinity maturation of antibody repertoires through iterative cycles of T-cell-dependent positive selection, B cell clonal expansion and antigen-receptor hypermutation. Positive selection is critical for efficient affinity maturation and depends on only partially understood signaling processes. We show that BCL6-dependent physiological repression of decay accelerating factor (DAF/CD55) on GC B cells is critical for effective positive selection and affinity maturation during GC responses. Absence of DAF on GC B cells lifts restraint on local complement activation, yielding autocrine C3a/C5a-receptor signaling that is indispensable for CD40-dependent mTOR pathway activation during positive selection. Genetic disruption of this pathway causes premature GC collapse and impairs affinity maturation. These results identify previously undiscerned targets to therapeutically manipulate protective and potentially injurious humoral immune responses.
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| Overall design |
Cg1-cre(+/-) or Cg1-cre(+/-);R26-DAF-TM(fl/fl) mice were immunized intraperitoneally with sheep red blood cells. Splenic germinal center B cells were sorted 10 days later for gene expression analysis.
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| Web link |
https://0-doi-org.brum.beds.ac.uk/10.1038/s41590-021-00926-0
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| |
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| Contributor(s) |
Dominguez-Sola D, Roberto MP, Hu Y |
| Citation(s) |
34031614 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 AI141434 |
Decay Accelerating Factor and B cell Immunity |
MOUNT SINAI SCHOOL OF MEDICINE |
David Dominguez-Sola |
| R01 AI141434 |
Decay Accelerating Factor and B cell Immunity |
MOUNT SINAI SCHOOL OF MEDICINE |
Peter Scott Heeger |
|
| Submission date |
Apr 13, 2020 |
| Last update date |
Jun 21, 2021 |
| Contact name |
David Dominguez-Sola |
| E-mail(s) |
david.dominguez-sola@mssm.edu
|
| Phone |
2128248432
|
| Organization name |
Icahn School of Medicine at Mount Sinai
|
| Department |
Oncological Sciences
|
| Street address |
One Gustave L. Levy Place, Box 1044A
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10029 |
| Country |
USA |
| |
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| Platforms (1) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA625050 |
| SRA |
SRP256282 |
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