BCL2 PROTEIN IS TOPOGRAPHICALLY RESTRICTED IN TISSUES CHARACTERIZED BY APOPTOTIC CELL-DEATH

BCL2 PROTEIN IS TOPOGRAPHICALLY RESTRICTED IN TISSUES CHARACTERIZED BY APOPTOTIC CELL-DEATH
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DOI:
10.1073/pnas.88.16.6961
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发表时间:
1991-08-01
影响因子:
11.1
通讯作者:
KORSMEYER, SJ
KORSMEYER, SJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
HOCKENBERY, DM;ZUTTER, M;KORSMEYER, SJ

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BCL 2原癌基因编码一种阻止程序性细胞死亡的线粒体内膜蛋白。从滤泡性B细胞淋巴瘤的染色体断裂点分离BCL 2。过表达BCL 2的转基因小鼠显示出静息B细胞的延长存活。在这项研究中,我们使用单特异性抗人BCL 2抗体来确定BCL 2蛋白在组织内的分布。BCL 2被限制在生发中心内的滤泡外套膜和涉及浆细胞和记忆B细胞的选择和维持的亮区的部分。BCL 2存在于胸腺髓质中存活的T细胞中。所有来源于更新干细胞的造血谱系也显示BCL 2。有限数量的非淋巴组织表现出BCL 2,并可分为(i)腺上皮,其中激素或生长因子调节增生和退化,(ii)复杂的分化上皮,如皮肤和肠,其特征是长寿命的干细胞,和(iii)长寿命的有丝分裂后细胞,如神经元。在这些表现出凋亡细胞更新的组织中,BCL 2通常在形貌上限于长寿命或增殖细胞区。BCL 2作为细胞凋亡的解毒剂的功能可以赋予这些组织中的祖细胞和效应细胞长寿。
The BCL2 protooncogene encodes an inner mitochondrial membrane protein that blocks programmed cell death. BCL2 was isolated from the chromosomal breakpoint of follicular B-cell lymphoma. Transgenic mice that overexpress BCL2 display extended survival of resting B cells. In this study we use a monospecific anti-human BCL2 antibody to define the distribution of BCL2 protein within organized tissues. BCL2 is restricted within germinal centers to the follicular mantle and to portions of the light zone implicated in the selection and maintenance of plasma cells and memory B cells. BCL2 is present in the surviving T cells in the thymic medulla. All hematopoietic lineages that derive from a renewing stem cell also display BCL2. A limited number of nonlymphoid tissues demonstrate BCL2 and can be grouped as (i) glandular epithelium in which hormones or growth factors regulate hyperplasia and involution, (ii) complex differentiating epithelium such as skin and intestine characterized by long-lived stem cells, and (iii) long-lived postmitotic cells such as neurons. Within these tissues that demonstrate apoptotic cell turnover, BCL2 is often topographically restricted to long-lived or proliferating cell zones. BCL2's function as an antidote to apoptosis may confer longevity to progenitor and effector cells in these tissues.