PI3K-mediated blimp-1 activation controls B cell selection and homeostasis
peer-reviewed
Erstveröffentlichung
2018-07-10Authors
Setz, Corinna S.
Hug, Eva
Khadour, Ahmad
Abdelrasoul, Hend
Bilal, Mayas
Wissenschaftlicher Artikel
Published in
Cell Reports ; 24 (2018), 2. - S. 391-405. - ISSN 2211-1247
Link to original publication
https://dx.doi.org/10.1016/j.celrep.2018.06.035Institutions
UKU. Institut für ImmunologieDocument version
published version (publisher's PDF)Abstract
Activation of phosphoinositide 3-kinase (PI3K) signaling plays a central role in regulating proliferation and survival of B cells. Here, we tested the hypothesis that B cell receptor (BCR)-mediated activation of PI3K induces the terminal differentiation factor Blimp-1 that interferes with proliferation and survival, thereby controlling the expansion of activated B cells. In fact, B-cell-specific inactivation of Pten, the negative regulator of PI3K signaling, leads to deregulated PI3K activity and elevated Blimp-1 expression. Combined deficiency for Pten and Blimp-1 results in abnormal expansion of B-1 B cells and splenomegaly. Interestingly, Blimp-1 also acts at early stages of B cell development to regulate B cell selection, as Blimp-1 deficiency results in an increased proportion of autoreactive B cells. Together, our data suggest that the combined requirement of deregulated PI3K signaling in addition to defective terminal differentiation represents the basis for proper selection and expansion of developing B cells.
EU Project uulm
Autonomous CLL-BCRs / Role of autonomous B cell receptor signalling and external antigen in the pathogenesis of chronic lymphocytic leukaemia (CLL) / EC / H2020 / 694992
DFG Project THU
SFB 1279 / Nutzung des menschlichen Peptidoms für die Entwicklung neuer antimikrobieller und anti-Krebs Therapeutika / DFG / 316249678
SFB 1074 / Experimentelle Modelle und klinische Translation bei Leukämien / DFG / 217328187
TRR 130 Teilprojekt 01 / Rolle der PI3K-Signale bei der Selektion und Überleben von B Zellen / DFG / 215346292
SFB 1074 / Experimentelle Modelle und klinische Translation bei Leukämien / DFG / 217328187
TRR 130 Teilprojekt 01 / Rolle der PI3K-Signale bei der Selektion und Überleben von B Zellen / DFG / 215346292
Is supplemented by
https://ars.els-cdn.com/content/image/1-s2.0-S2211124718309458-mmc1.pdfhttps://ars.els-cdn.com/content/image/1-s2.0-S2211124718309458-mmc2.pdf
Subject headings
[GND]: Proliferation | Auslese | PTEN Phosphohydrolase[LCSH]: Editing
[Free subject headings]: autoreactivity | B cell development | selection | editing | clonal deletion differentiation | Pten | Blimp-1
[DDC subject group]: DDC 570 / Life sciences
Metadata
Show full item recordDOI & citation
Please use this identifier to cite or link to this item: http://dx.doi.org/10.18725/OPARU-48998
Setz, Corinna S. et al. (2023): PI3K-mediated blimp-1 activation controls B cell selection and homeostasis. Open Access Repositorium der Universität Ulm und Technischen Hochschule Ulm. http://dx.doi.org/10.18725/OPARU-48998
Citation formatter >