| First Author | Sintes J | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 1462 |
| PubMed ID | 29133782 | Mgi Jnum | J:257210 |
| Mgi Id | MGI:6106108 | Doi | 10.1038/s41467-017-01602-4 |
| Citation | Sintes J, et al. (2017) mTOR intersects antibody-inducing signals from TACI in marginal zone B cells. Nat Commun 8(1):1462 |
| abstractText | Mechanistic target of rapamycin (mTOR) enhances immunity in addition to orchestrating metabolism. Here we show that mTOR coordinates immunometabolic reconfiguration of marginal zone (MZ) B cells, a pre-activated lymphocyte subset that mounts antibody responses to T-cell-independent antigens through a Toll-like receptor (TLR)-amplified pathway involving transmembrane activator and CAML interactor (TACI). This receptor interacts with mTOR via the TLR adapter MyD88. The resulting mTOR activation instigates MZ B-cell proliferation, immunoglobulin G (IgG) class switching, and plasmablast differentiation through a rapamycin-sensitive pathway that integrates metabolic and antibody-inducing transcription programs, including NF-kappaB. Disruption of TACI-mTOR interaction by rapamycin, truncation of the MyD88-binding domain of TACI, or B-cell-conditional mTOR deficiency interrupts TACI signaling via NF-kappaB and cooperation with TLRs, thereby hampering IgG production to T-cell-independent antigens but not B-cell survival. Thus, mTOR drives innate-like antibody responses by linking proximal TACI signaling events with distal immunometabolic transcription programs. |
