mTOR intersects antibody-inducing signals from TACI in marginal zone B cells

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-κB. 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-κB 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.

Ingår i:Nature communications: Springer Science and Business Media LLC8:1, s. 1462-2041-1723

Av författaren/redakt...: Sintes, J; Gentile, M; Zhang, SL; Garcia-Carmona, ...; Magri, G; Cassis, L; visa fler...; Segura-Garzon, D; Ciociola, A; Grasset, EK; Bascones, S; Comerma, L; Pybus, M; Llige, D; Puga, I; Gutzeit, C; He, B; DuBois, W; Crespo, M; Pascual, J; Mensa, A; Arostegui, JI; Juan, M; Yague, J; Serrano, S; Lloreta, J; Meffre, E; Hahne, M; Cunningham-Rundl ...; Mock, BA; Cerutti, A; visa färre...

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