Journal of Immunology 2009-04-15

Inositol 1,4,5-trisphosphate 3-kinase B is a negative regulator of BCR signaling that controls B cell selection and tolerance induction.

Andrew T Miller, Daniel R Beisner, Daorong Liu, Michael P Cooke

Index: J. Immunol. 182(8) , 4696-704, (2009)

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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.