title: Inositol 1,4,5-trisphosphate 3-kinase B is a negative regulator of BCR signaling that controls B cell selection and tolerance induction.
abstract: Inositol 1,4,5-trisphosphate 3-kinase B (or Itpkb) converts inositol 1,4,5-trisphosphate to inositol 1,3,4,5-tetrakisphosphate upon Ag receptor activation and controls the fate and function of lymphocytes. To determine the role of Itpkb in B cell tolerance, Itpkb(-/-) mice were crossed to transgenic mice that express a BCR specific for hen egg lysozyme (IgHEL). B cells from Itpkb(-/-) IgHEL mice possess an anergic phenotype, hypoproliferate in response to cognate Ag, and yet they exhibit enhanced Ag-induced calcium signaling. In IgHEL transgenic mice that also express soluble HEL, lack of Itpkb converts anergy induction to deletion. These data establish Itpkb as a negative regulator of BCR signaling that controls the fate of developing B cells and tolerance induction.
authors.affiliation: The Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Miller
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Beisner
authors.forename: Daorong
authors.initials: D
authors.lastname: Liu
authors.forename: Michael P
authors.initials: MP
authors.lastname: Cooke