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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Santos, Margarida Almeida Demengeot, Jocelyne Maillard, Ivan Rebelo, Manuel Sarmento, Leonor Morais Radtke, Freddy Doce, Ana Agua Neves, Helia Parreira, Leonor Pear, Warren S. Dumortier, Alexis |
| Description | Author Affiliation: Santos MA ( Instituto Gulbenkian de Ciência, 2781-901 Oeiras, Portugal.); |
| Abstract | 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-Dll1 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 39 |
| Volume Number | 104 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2007-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | B-Lymphocytes Metabolism Intracellular Signaling Peptides And Proteins Genetics Membrane Proteins Receptor, Notch1 Physiology Animals Calcium-Binding Proteins Cell Differentiation Dose-Response Relationship, Drug Immunoglobulins Intercellular Signaling Peptides And Proteins Ligands Lipopolysaccharides Chemistry Mice Mice, Inbred C57BL Receptors, Notch Spleen Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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