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

作者：Sintes Jordi^*; Gentile Maurizio; Zhang Shuling; Garcia Carmona Yolanda; Magri Giuliana; Cassis Linda; Segura Garzon Daniel; Ciociola Alessandra; Grasset Emilie K; Bascones Sabrina; Comerma Laura; Pybus Marc; Llige David; Puga Irene; Gutzeit Cindy; He Bing; DuBois Wendy; Crespo Marta; Pascual Julio; Mensa Anna; Ignacio Arostegui Juan; Juan Manel; Yague Jordi; Serrano Sergi; Lloreta Josep; Meffre Eric; Hahne Michael; Cunningham Rundles Charlotte; Mock Beverly A

来源：Nature Communications, 2017, 8(1): 1462.

DOI：10.1038/s41467-017-01602-4

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-kappa B. 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-kappa B 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.

• 出版日期2017-11-13
• 单位NIH