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

作者：Santos Margarida Almeida; Sarmento Leonor Morais; Rebelo Manuel; Doce Ana Agua; Maillard Ivan; Durnortier Alexis; Neves Helia; Radtke Freddy; Pear Warren S; Parreira Leonor; Demengeot Jocelyne^*

来源：Proceedings of the National Academy of Sciences, 2007, 104(39): 15454-15459.

DOI：10.1073/pnas.0702891104

• activation
• B cells
• immunoglobulin
• commitment
• LPS

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 LIPS or anti-CD40 when provided exogenous Notch ligand Delta-like-1 (DII1). Our results indicate that Notch-Dill interaction releases a default pathway that otherwise inhibits Ig secretion upon B cell activation. Thus, Dill 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 Dill-mediated enhancement of ASC differentiation but also reduced dramatically LPS-induced Ig secretion. Finally, we show that Dill 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.

• 出版日期2007-9-25
• 单位河北医科大学