{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T21:58:32Z","timestamp":1762898312483},"reference-count":30,"publisher":"Proceedings of the National Academy of Sciences","issue":"39","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,9,25]]},"abstract":"<jats:p>Notch signaling regulates B and T lymphocyte development and T cell effector class decision. In this work, we tested whether Notch activity affects mature B cell activation and differentiation to antibody-secreting cells (ASC). We show increased frequency of ASC in cultures of splenic B cells activated with LPS or anti-CD40 when provided exogenous Notch ligand Delta-like-1 (Dll1). Our results indicate that Notch\u2013Dll1 interaction releases a default pathway that otherwise inhibits Ig secretion upon B cell activation. Thus, Dll1 enhanced spontaneous Ig secretion by naturally activated marginal zone B and B1 cells and reversed the inhibition of ASC differentiation mediated by B cell receptor crosslinking during LPS. Moreover, suppression of Notch signaling in B cell expression of either a dominant-negative mutant form of Mastermind-like 1 or a null mutation of Notch1 not only prevented Dll1-mediated enhancement of ASC differentiation but also reduced dramatically LPS-induced Ig secretion. Finally, we show that Dll1 and Jagged-1 are differentially expressed in discrete areas of the spleen, and that the effect of Notch engagement on Ig secretion is ligand-specific. These results indicate that Notch ligands participate in the definition of the mature B cell microenvironment that influences their terminal differentiation.<\/jats:p>","DOI":"10.1073\/pnas.0702891104","type":"journal-article","created":{"date-parts":[[2007,9,19]],"date-time":"2007-09-19T01:04:45Z","timestamp":1190163885000},"page":"15454-15459","update-policy":"http:\/\/dx.doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":82,"title":["Notch1 engagement by Delta-like-1 promotes differentiation of B lymphocytes to antibody-secreting cells"],"prefix":"10.1073","volume":"104","author":[{"given":"Margarida Almeida","family":"Santos","sequence":"first","affiliation":[{"name":"*Instituto Gulbenkian de Ci\u00eancia, 2781-901 Oeiras, Portugal;"}]},{"given":"Leonor Morais","family":"Sarmento","sequence":"additional","affiliation":[{"name":"*Instituto Gulbenkian de Ci\u00eancia, 2781-901 Oeiras, Portugal;"}]},{"given":"Manuel","family":"Rebelo","sequence":"additional","affiliation":[{"name":"*Instituto Gulbenkian de Ci\u00eancia, 2781-901 Oeiras, Portugal;"}]},{"given":"Ana Agua","family":"Doce","sequence":"additional","affiliation":[{"name":"*Instituto Gulbenkian de Ci\u00eancia, 2781-901 Oeiras, Portugal;"}]},{"given":"Ivan","family":"Maillard","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2013Oncology and"}]},{"given":"Alexis","family":"Dumortier","sequence":"additional","affiliation":[{"name":"Swiss Institute for Experimental Cancer Research and Swiss Federal Institute of Technology Lausanne, 1066 Epalinges, Switzerland; and"}]},{"given":"Helia","family":"Neves","sequence":"additional","affiliation":[{"name":"*Instituto Gulbenkian de Ci\u00eancia, 2781-901 Oeiras, Portugal;"},{"name":"Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal"}]},{"given":"Freddy","family":"Radtke","sequence":"additional","affiliation":[{"name":"Swiss Institute for Experimental Cancer Research and Swiss Federal Institute of Technology Lausanne, 1066 Epalinges, Switzerland; and"}]},{"given":"Warren S.","family":"Pear","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute and Institute for Medicine and Engineering, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;"}]},{"given":"Leonor","family":"Parreira","sequence":"additional","affiliation":[{"name":"*Instituto Gulbenkian de Ci\u00eancia, 2781-901 Oeiras, Portugal;"},{"name":"Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal"}]},{"given":"Jocelyne","family":"Demengeot","sequence":"additional","affiliation":[{"name":"*Instituto Gulbenkian de Ci\u00eancia, 2781-901 Oeiras, 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