Institut de Recherches Interdisciplinaires en Biologie Humaine et Moléculaire (IRIBHM), Institut de Biologie et de Médecine Moléculaires (IBMM), Faculté de Médecine, Université Libre de Bruxelles, Gosselies, Belgium.
Immunobiology. 2011 Jan-Feb;216(1-2):103-9. doi: 10.1016/j.imbio.2010.03.012. Epub 2010 Apr 14.
Inositol 1,4,5-trisphosphate 3-kinase B (or Itpkb) and inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), its reaction product, play an important role in the control of B lymphocyte fate and function in vivo. In order to investigate the fine mechanisms of Itpkb and Ins(1,3,4,5)P4 action in B cells, we crossed Itpkb(-/-) mice with transgenic mice expressing a 3-83μδ B cell receptor (BCR) specific for membrane-bound MHC-I H2-K(b) and H2-K(k) molecules. On a non-deleting H2-K(d) genetic background, we show that Itpkb is important for the control of Bim protein expression and B cell survival rather than for the control of B cell development from one stage to another. Analyses of cell surface markers expression, proapoptotic Bim protein expression, in vitro survival and in vivo turnover demonstrated that BCR transgenic Itpkb(-/-) B cells exhibit an anergic phenotype with the notable exception of their enhanced antigen-induced calcium signalling. On a deleting H2-K(b) genetic background, we show that Itpkb is not essential for BCR editing or negative selection. These data establish Itpkb as an important regulator of B cell survival and anergy in vivo.
肌醇 1,4,5-三磷酸 3-激酶 B（或 Itpkb）及其反应产物肌醇 1,3,4,5-四磷酸（Ins(1,3,4,5)P4）在体内控制 B 淋巴细胞命运和功能中发挥重要作用。为了研究 Itpkb 和 Ins(1,3,4,5)P4 在 B 细胞中的精细作用机制，我们将 Itpkb(-/-) 小鼠与表达针对膜结合 MHC-I H2-K(b)和 H2-K(k)分子的 3-83μδ B 细胞受体（BCR）的转基因小鼠进行杂交。在非缺失 H2-K(d)遗传背景下，我们表明 Itpkb 对于控制 Bim 蛋白表达和 B 细胞存活很重要，而不是控制 B 细胞从一个阶段到另一个阶段的发育。对细胞表面标志物表达、促凋亡 Bim 蛋白表达、体外存活和体内周转率的分析表明，BCR 转基因 Itpkb(-/-)B 细胞表现出无反应表型，但其抗原诱导的钙信号显著增强。在缺失 H2-K(b)遗传背景下，我们表明 Itpkb 对于 BCR 编辑或负选择不是必需的。这些数据确立了 Itpkb 作为体内 B 细胞存活和无反应的重要调节剂。
