Notch signaling suppresses IgH gene expression in chicken B cells: Implication in spatially restricted expression of Serrate2/Notch1 in the bursa of Fabricius

The bursa of Fabricius is a central organ for chicken B cell development an d provides an essential microenvironment for expansion of the B cell pool a nd for generation of a diversified B cell repertoire. We report here that g enes encoding the Notch family of transmembrane proteins, key regulators of cell fate determination in development, are differentially expressed in th e bursa of Fabricius: Notch1 is expressed in medullary B cells located clos e to the basement membrane-associated epithelium (BMAE), In contrast, a Not ch ligand, Serrate2, is expressed exclusively in the BMAE, which surrounds bursal medulla, A basic helix-loop-helix-type transcription factor, Hairy1, a downstream target of Notch signaling, is expressed in the bursa coordina tely with Notch1 and Serrate2 and an immature B cell line, TLT1, which expr esses both Notch1 and Serrate2, Furthermore, stable expression of a constit utively active form of chicken Notch1 or Notch2 in a B cell line results in a down-regulation of surface IgM expression, which is accompanied by the r eduction of IgH gene transcripts. Transient reporter assay with the human I gH gene intronic enhancer reveals that an active form of Notch1 inhibits th e IgH enhancer activity in chicken B cells, suggesting that Notch-mediated signals suppress the IgH gene expression via influencing the IgH intronic e nhancer. These findings raise the possibility that the local activation of Notch1 in a subset of B cells by Serrate2 expressed in BMAE may influence t he cell fate decision that is involved in B cell differentiation and select ion inside the bursa.