Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85α
Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85α
复制标题
DOI：
10.1126/science.283.5400.393
复制
发表时间：
1999-01-15
期刊：
影响因子：
56.9
通讯作者：
Cantley, LC
中科院分区：
文献类型：
--
作者：
Fruman, DA;Snapper, SB;Cantley, LC
磷酸肌醇3-激酶（PI3K）激活已与许多细胞反应有关，包括成纤维细胞生长，转化，生存，生存和趋化性，尽管PI3K激活了几种刺激T和B细胞的药物，但PI3K在淋巴细胞功能中的作用并非清除。编码PI3K适配器亚基p85 alpha及其剪接变体p55 alpha和p50 alpha的小鼠基因被破坏。大多数P85 alpha-p55 alpha-p50α（ - / - ）小鼠在出生后几天死亡。通过使用RAG2缺陷型胚泡互补系统研究了淋巴细胞的发育和功能。嵌合小鼠的周围成熟B细胞数量减少，血清免疫球蛋白减少。开发的B细胞减少了对对免疫球蛋白M，抗CD40抗体和脂多糖刺激的抗体的增殖反应，与介绍与白云细胞A孵育后，T细胞发育和增殖均为正常。这种表型类似于缺乏酪氨酸激酶BTK的小鼠中观察到的缺陷。
Phosphoinositide 3-kinase (PI3K) activation has been implicated in many cellular responses, including fibroblast growth, transformation, survival, and chemotaxis, Although PI3K is activated by several agents that stimulate T and B cells, the role of PI3K in Lymphocyte function is not clear. The mouse gene encoding the PI3K adapter subunit p85 alpha and its splice variants p55 alpha and p50 alpha was disrupted. Most p85 alpha-p55 alpha-p50 alpha(-/-) mice die within days after birth. Lymphocyte development and function was studied with the use of the RAG2-deficient blastocyst complementation system. Chimeric mice had reduced numbers of peripheral mature B cells and decreased serum immunoglobulin. The B cells that developed had diminished proliferative responses to antibody to immunoglobulin M, antibody to CD40, and Lipopolysaccharide stimulation and decreased survival after incubation with interleukin-A In contrast, T cell development and proliferation was normal. This phenotype is similar to defects observed in mice lacking the tyrosine kinase Btk.