{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T13:57:20Z","timestamp":1768485440872,"version":"3.49.0"},"posted":{"date-parts":[[2019,11,21]]},"group-title":"Immunology","reference-count":49,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2019,11,21]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Persistence of long-lived, memory plasma cells in the bone marrow depends on survival factors available in the bone marrow, provided in niches organized by stromal cells. Here we describe that\n                  <jats:italic>ex vivo<\/jats:italic>\n                  we can prevent apoptosis of bone marrow plasma cells by supplying direct cell contact with stromal cells and the soluble cytokine APRIL. Integrin-mediated contact of bone marrow plasma cells with stromal cells activates the PI3K signaling pathway, leading to critical inactivation of FoxO1\/3 and preventing the activation of mitochondrial stress-associated effector caspases 3 and 7. Likely, inhibition of PI3K signaling\n                  <jats:italic>in vivo<\/jats:italic>\n                  ablates bone marrow plasma cells. APRIL signaling, via the NF-\u03baB pathway, blocks activation of the endoplasmic reticulum stress-associated initiator caspase 12. Thus, stromal cell-contact induced PI3K and APRIL-induced NF-\u03baB signaling provide necessary and complementary signals to maintain bone marrow memory plasma cells.\n                <\/jats:p>","DOI":"10.1101\/849638","type":"posted-content","created":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T19:16:06Z","timestamp":1574363766000},"source":"Crossref","is-referenced-by-count":1,"title":["Stromal cell-contact dependent PI3K and APRIL induced NF-\u03baB signaling complement each other to prevent mitochondrial- and endoplasmic reticulum stress induced cell death of bone marrow plasma cells"],"prefix":"10.64898","author":[{"given":"Rebecca","family":"Cornelis","sequence":"first","affiliation":[]},{"given":"Stefanie","family":"Hahne","sequence":"additional","affiliation":[]},{"given":"Adriano","family":"Taddeo","sequence":"additional","affiliation":[]},{"given":"Georg","family":"Petkau","sequence":"additional","affiliation":[]},{"given":"Darya","family":"Malko","sequence":"additional","affiliation":[]},{"given":"Pawel","family":"Durek","sequence":"additional","affiliation":[]},{"given":"Manja","family":"Thiem","sequence":"additional","affiliation":[]},{"given":"Lukas","family":"Heiberger","sequence":"additional","affiliation":[]},{"given":"Elodie","family":"Mohr","sequence":"additional","affiliation":[]},{"given":"Cora","family":"Klaeden","sequence":"additional","affiliation":[]},{"given":"Koji","family":"Tokoyoda","sequence":"additional","affiliation":[]},{"given":"Francesco","family":"Siracusa","sequence":"additional","affiliation":[]},{"given":"Bimba Franziska","family":"Hoyer","sequence":"additional","affiliation":[]},{"given":"Falk","family":"Hiepe","sequence":"additional","affiliation":[]},{"given":"Mir-Farzin","family":"Mashreghi","sequence":"additional","affiliation":[]},{"given":"Fritz","family":"Melchers","sequence":"additional","affiliation":[]},{"given":"Hyun-Dong","family":"Chang","sequence":"additional","affiliation":[]},{"given":"Andreas","family":"Radbruch","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"key":"2019112306350411000_849638v1.1","doi-asserted-by":"crossref","unstructured":"Addo, R. 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