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| Status |
Public on Feb 04, 2020 |
| Title |
Serine/Threonine phosphatase PP2A is essential for optimal B cell function |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Protein phosphatase 2A (PP2A), a serine/threonine phosphatase, has been shown to control T cell function. We found that in vitro activated B cells and B cells from various lupus-prone mice and patients with systemic lupus erythematosus display increased PP2A activity. To understand the contribution of PP2A to B cell function, we generated a Cd19CrePpp2r1aflox/flox (flox/flox) mouse which lacks functional PP2A only in B cells. Flox/flox mice displayed reduced spontaneous germinal center formation and decreased responses to T-dependent and T-independent antigens while their B cells responded poorly in vitro to stimulation with an anti-CD40 antibody or CpG in the presence of IL-4. Transcriptome and metabolome studies revealed altered NAD and purine/pyrimidine metabolism and increased expression of purine nucleoside phosphorylase in PP2A-deficient B cells. Our results demonstrate that PP2A is required for optimal B cell function and may contribute to increased B cell activity in systemic autoimmunity.
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| Overall design |
Examination of gene expression in B cells from 1) wild-type mice 2) B cell-specific PP2Aa-deficient mice
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| |
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| Contributor(s) |
Tsokos GC, Li H |
| Citation(s) |
32161189 |
| |
| Submission date |
Feb 03, 2020 |
| Last update date |
Apr 13, 2020 |
| Contact name |
George C Tsokos |
| E-mail(s) |
gtsokos@bidmc.harvard.edu
|
| Phone |
(617) 632-8658
|
| Organization name |
Harvard Medical School
|
| Department |
Rheumatology/BIDMC
|
| Street address |
CLS-928, 3 Blackfan Circle
|
| City |
Boston |
| State/province |
Massachusetts |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (6)
|
| GSM4294001 |
PP2Aa deficient B cells [000008518869_C02] |
| GSM4294002 |
PP2Aa deficient B cells [000008518869_C03] |
| GSM4294003 |
PP2Aa deficient B cells [000008518869_C04] |
|
| Relations |
| BioProject |
PRJNA604601 |
| SRA |
SRP246937 |
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