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Notch1 engagement by Delta-like-1 promotes differentiation of B lymphocytes to antibody-secreting cells.


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.

SUBMITTER: Santos MA 

PROVIDER: S-EPMC2000509 | biostudies-literature | 2007 Sep

REPOSITORIES: biostudies-literature

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Notch1 engagement by Delta-like-1 promotes differentiation of B lymphocytes to antibody-secreting cells.

Santos Margarida Almeida MA   Sarmento Leonor Morais LM   Rebelo Manuel M   Doce Ana Agua AA   Maillard Ivan I   Dumortier Alexis A   Neves Helia H   Radtke Freddy F   Pear Warren S WS   Parreira Leonor L   Demengeot Jocelyne J  

Proceedings of the National Academy of Sciences of the United States of America 20070918 39


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 upo  ...[more]

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