biostudies-literatureUnknown104(35)Marechal YThe contribution of the B isoform of inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] 3-kinase (or Itpkb) and inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P(4)], its reaction product, to B cell function and development remains unknown. Here, we show that mice deficient in Itpkb have defects in B cell survival leading to specific and intrinsic developmental alterations in the B cell lineage and antigen unresponsiveness in vivo. The decreased B cell survival is associated with a decreased phosphorylation of Erk1/2 and increased Bim gene expression. B cell survival, development, and antigen responsiveness are normalized in parallel to reduced expression of Bim in Itpkb(-/-) Bim(+/-) mice. Analysis of the signaling pathway downstream of Itpkb revealed that Ins(1,3,4,5)P(4) regulates subcellulaProceedings of the National Academy of Sciences of the United States of America13978-83https://www.ebi.ac.uk/biostudies/studies/S-EPMC1955816biostudies-literatureInositol 1,3,4,5-tetrakisphosphate controls proapoptotic Bim gene expression and survival in B cells.PMC1955816Pouillon VLuo HRDaniel JSchurmans SMarechal YIzui SJia YPerez-Morga DErneux CLeo OPesesse XCullen PJfalseInositol 1,3,4,5-tetrakisphosphate controls proapoptotic Bim gene expression and survival in B cells.The contribution of the B isoform of inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] 3-kinase (or Itpkb) and inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P(4)], its reaction product, to B cell function and development remains unknown. Here, we show that mice deficient in Itpkb have defects in B cell survival leading to specific and intrinsic developmental alterations in the B cell lineage and antigen unresponsiveness in vivo. The decreased B cell survival is associated with a decreased phosphorylation of Erk1/2 and increased Bim gene expression. B cell survival, development, and antigen responsiveness are normalized in parallel to reduced expression of Bim in Itpkb(-/-) Bim(+/-) mice. Analysis of the signaling pathway downstream of Itpkb revealed that Ins(1,3,4,5)P(4) regulates subcellula2007-01-01T00:00:00Z2007 Aug2026-03-16T16:43:09.223Z2019-03-27T02:21:26ZS-EPMC19558161770975110.1073/pnas.0704312104