{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:17:27Z","timestamp":1792736247654,"version":"4.5.0"},"reference-count":63,"publisher":"Rockefeller University Press","issue":"10","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,11,21]]},"abstract":"<jats:p>The B cell activating factor belonging to the tumor necrosis factor family (BAFF) is required for B cell survival and maturation. The mechanisms by which BAFF mediates B cell survival are less understood. We found that BAFF and a proliferation-inducing ligand (APRIL), which are related, block B cell antigen receptor (BCR)\u2013induced apoptosis upstream of mitochondrial damage, which is consistent with a role for Bcl-2 family proteins. BCR ligation strongly increased expression of the proapoptotic Bcl-2 homology 3\u2013only Bcl-2 protein Bim in both WEHI-231 and splenic B cells, and increases in Bim were reversed by BAFF or APRIL. Small interfering RNA vector\u2013mediated suppression of Bim blocked BCR-induced apoptosis. BAFF also induced Bim phosphorylation and inhibited BCR-induced association of Bim with Bcl-2. BAFF induced delayed but sustained stimulation of extracellular signal\u2013regulated kinase (ERK) and its activators, mitogen-activated protein kinase\/ERK activating kinase (MEK) and c-Raf, and MEK inhibitors promoted accumulation and dephosphorylation of Bim. These results suggest that BAFF inhibits BCR-induced death by down-regulating Bim via sustained ERK activation, demonstrating that BAFF directly regulates Bim function. Although transitional immature type 1 (T1) B cell numbers are normal in Bim\u2212\/\u2212 mice, T2 and follicular mature B cells are elevated and marginal zone B cells are reduced. Our results suggest that mature B cell homeostasis is maintained by BAFF-mediated regulation of Bim.<\/jats:p>","DOI":"10.1084\/jem.20051283","type":"journal-article","created":{"date-parts":[[2005,11,21]],"date-time":"2005-11-21T19:19:18Z","timestamp":1132600758000},"page":"1363-1374","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":161,"title":["BAFF regulates B cell survival by downregulating the BH3-only family member Bim via the ERK pathway"],"prefix":"10.1084","volume":"202","author":[{"given":"Andrew","family":"Craxton","sequence":"first","affiliation":[{"name":"1Department of Microbiology, University of Washington, Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin E.","family":"Draves","sequence":"additional","affiliation":[{"name":"1Department of Microbiology, University of Washington, Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Gruppi","sequence":"additional","affiliation":[{"name":"2Department of Immunology, University of Washington, Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward A.","family":"Clark","sequence":"additional","affiliation":[{"name":"1Department of Microbiology, University of Washington, Seattle, WA 98195"},{"name":"2Department of Immunology, University of Washington, Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2005,11,21]]},"reference":[{"key":"2023072513014611000_BIB1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1146\/annurev.immunol.21.120601.141029","volume":"21","year":"2003","journal-title":"Annu. 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