biostudies-literatureGaudette BTNIAID NIH HHSNCI NIH HHSNIAIDe151975https://www.ebi.ac.uk/biostudies/studies/S-EPMC8516456biostudies-literatureUnknown131(20)Little is known about how cells regulate and integrate distinct biosynthetic pathways governing differentiation and cell division. For B lineage cells it is widely accepted that activated cells must complete several rounds of mitosis before yielding antibody-secreting plasma cells. However, we report that marginal zone (MZ) B cells, innate-like naive B cells known to generate plasma cells rapidly in response to blood-borne bacteria, generate functional plasma cells despite cell-cycle arrest. Further, short-term Notch2 blockade in vivo reversed division-independent differentiation potential and decreased transcript abundance for numerous mTORC1- and Myc-regulated genes. Myc loss compromised plasma cell differentiation for MZ B cells, and reciprocally induced ectopic mTORC1 signaling in follThe Journal of clinical investigationResting innate-like B cells leverage sustained Notch2/mTORC1 signaling to achieve rapid and mitosis-independent plasma cell differentiation.PMC8516456R01 AI091627T32 CA009140AI154932R01 AI154932AI139123R01 AI139123Ochoa TASiebel CWRoman CJJones DDAllman DGomez Atria DMaillard IGaudette BTfalseResting innate-like B cells leverage sustained Notch2/mTORC1 signaling to achieve rapid and mitosis-independent plasma cell differentiation.Little is known about how cells regulate and integrate distinct biosynthetic pathways governing differentiation and cell division. For B lineage cells it is widely accepted that activated cells must complete several rounds of mitosis before yielding antibody-secreting plasma cells. However, we report that marginal zone (MZ) B cells, innate-like naive B cells known to generate plasma cells rapidly in response to blood-borne bacteria, generate functional plasma cells despite cell-cycle arrest. Further, short-term Notch2 blockade in vivo reversed division-independent differentiation potential and decreased transcript abundance for numerous mTORC1- and Myc-regulated genes. Myc loss compromised plasma cell differentiation for MZ B cells, and reciprocally induced ectopic mTORC1 signaling in foll2021-01-01T00:00:00Z2021 Oct2026-05-08T09:00:41.218Z2022-02-11T16:18:22.409ZS-EPMC85164563447365110.1172/JCI15197510.1172/jci151975