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Usage Information

mTOR has distinct functions in generating versus sustaining humoral immunity
Derek D. Jones, … , Brendan M. Weiss, David Allman
Derek D. Jones, … , Brendan M. Weiss, David Allman
Published October 17, 2016
Citation Information: J Clin Invest. 2016;126(11):4250-4261. https://doi.org/10.1172/JCI86504.
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Research Article Immunology

mTOR has distinct functions in generating versus sustaining humoral immunity

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Abstract

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 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, and both strategies led to the ablation of newly formed plasma cells in the spleen and bone marrow while also obliterating preexisting 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.

Authors

Derek D. Jones, Brian T. Gaudette, Joel R. Wilmore, Irene Chernova, Alexandra Bortnick, Brendan M. Weiss, David Allman

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Usage data is cumulative from July 2024 through July 2025.

Usage JCI PMC
Text version 787 136
PDF 107 52
Figure 471 3
Supplemental data 62 1
Citation downloads 89 0
Totals 1,516 192
Total Views 1,708
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