{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T03:22:11Z","timestamp":1769656931765,"version":"3.49.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2007,1,1]],"date-time":"2007-01-01T00:00:00Z","timestamp":1167609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Deficiency in the adaptor protein B cell linker protein (BLNK) results in a substantial but incomplete block in B cell development, suggesting that alternative pathways exist for B lineage differentiation. Another adaptor protein, c-Cbl, plays a negative regulatory role in several BCR-signaling pathways. We therefore investigated the role of c-Cbl during B cell development and addressed the possibility that redundancies in pathways for B cell differentiation could be further revealed by eliminating negative effects mediated by c-Cbl. Strikingly, c-Cbl inactivation reversed a number of the critical defects in early B cell differentiation that are seen in BLNK-deficient mice. c-Cbl\u2212\/\u2212BLNK\u2212\/\u2212 mice exhibited normalized down-regulation of pre-BCR and CD43, up-regulation of MHC class II, and augmented L chain rearrangement, resulting in a successful transition from pre-B cells to immature B cells. c-Cbl inactivation also reversed the potentially tumor-predisposing hyperproliferative response of BLNK\u2212\/\u2212 pre-B cells to IL-7. Pre-BCR cross-linking induced enhanced and prolonged tyrosine phosphorylation in c-Cbl\u2212\/\u2212BLNK\u2212\/\u2212 pre-BCR+ pre-B cells compared with c-Cbl+\/\u2212BLNK\u2212\/\u2212 cells, including elevated phosphorylation of Lyn, Syk, Btk, and phospholipase C-\u03b32. Our studies suggest that some, but not all, pre-BCR-triggered developmental events can be mediated by BLNK-independent pathways that are negatively regulated by c-Cbl, and further suggest that different events during early B cell development require different strength or duration of pre-BCR signaling.<\/jats:p>","DOI":"10.4049\/jimmunol.178.2.926","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:17:51Z","timestamp":1397848671000},"page":"926-935","source":"Crossref","is-referenced-by-count":5,"title":["Redundancy in B Cell Developmental Pathways: c-Cbl Inactivation Rescues Early B Cell Development through a B Cell Linker Protein-Independent Pathway"],"prefix":"10.1093","volume":"178","author":[{"given":"Haifeng","family":"Song","sequence":"first","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y Jeffrey","family":"Chiang","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reuben P","family":"Siraganian","sequence":"additional","affiliation":[{"name":"Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J","family":"Hodes","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute , Bethesda, MD 20892"},{"name":"National Institute on Aging, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2007,1,15]]},"reference":[{"key":"2026012809421725800_R1","first-page":"1725","volume-title":"J. 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