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| Status |
Public on Sep 20, 2016 |
| Title |
mTOR has distinct functions in generating versus sustaining humoral immunity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Little is known about the role of mTOR signaling in plasma cell differentiation and function. Furthermore, for reasons not understood, mTOR inhibition reverses antibody-associated disease in a murine model of systemic lupus erythematosus. Here, we have demonstrated that induced B-lineage specific deletion of the gene encoding RAPTOR, an essential signaling adaptor for the rapamycin-sensitive mTOR complex 1 (mTORC1) abrogated the generation of antibody-secreting plasma cells in mice. Acute treatment with rapamycin recapitulated the effects of RAPTOR deficiency, while both strategies led to the ablation of newly formed plasma cells in the spleen and bone marrow while also obliterating pre-existing germinal centers. Surprisingly, although perturbing mTOR activity caused a profound decline in serum antibodies that were specific for exogenous antigen or DNA, frequencies of long-lived bone marrow plasma cells were unaffected. Instead, mTORC1 inhibition led to decreased expression of immunoglobulin binding protein (BiP) and other factors needed for robust protein synthesis. Consequently, blockade of antibody synthesis was rapidly reversed after termination of rapamycin treatment. We conclude that mTOR signaling plays critical but diverse roles in early and late phases of antibody responses and plasma cell differentiation.
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| Overall design |
B6.BLIMP1 +/GFP mice were untreated or treated with rapamycin. RNA isolated from FACS-sorted B220-negative Blimp1-positive bone marrow plasma cells was subjected to microarray analysis. Five mice were used per group.
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| Contributor(s) |
Jones DD, Gaudette BT, Wilmore JR, Chernova I, Bortnick A, Weiss BM, Allman DM |
| Citation(s) |
27760048 |
| Submission date |
Sep 16, 2016 |
| Last update date |
Jun 26, 2019 |
| Contact name |
Brian Thomas Gaudette |
| Organization name |
University of Pennsylvania
|
| Department |
Pathology and Lab Medicine
|
| Lab |
Brian Gaudette
|
| Street address |
3620 Hamilton Walk, Pathology and Laboratory Medicine
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (10)
|
| GSM2319234 |
Blimp1-positive plasma cell untreated rep1 |
| GSM2319235 |
Blimp1-positive plasma cell untreated rep2 |
| GSM2319236 |
Blimp1-positive plasma cell untreated rep3 |
| GSM2319237 |
Blimp1-positive plasma cell untreated rep4 |
| GSM2319238 |
Blimp1-positive plasma cell untreated rep5 |
| GSM2319239 |
Blimp1-positive plasma cell rapamycin rep1 |
| GSM2319240 |
Blimp1-positive plasma cell rapamycin rep2 |
| GSM2319241 |
Blimp1-positive plasma cell rapamycin rep3 |
| GSM2319242 |
Blimp1-positive plasma cell rapamycin rep4 |
| GSM2319243 |
Blimp1-positive plasma cell rapamycin rep5 |
|
| Relations |
| BioProject |
PRJNA343558 |
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