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Immunity:发现控制B淋巴细胞发育的代谢检查点

来源:生物谷 2012-05-21 22:14

近日,来自华盛顿大学的研究人员表示,他们发现了控制B淋巴细胞发育的一个代谢检查点,即卵巢滤泡激素相互作用蛋白1(Fnip1)。相关研究成果于5月17日在线发表在Immunity上。

协调好体内代谢与细胞的生长及分裂之间的关系,对免疫细胞的正常发育及功能至关重要。

最近,Brian M. Iritani等人利用化学诱变方法,得到了一种特殊的小鼠品系,他们发现,这种小鼠的B淋巴细胞在初始B细胞阶段的发育受到阻碍,进一步研究发现,这是因为该种小鼠缺失了Fnip1基因的缘故。

然而,利用转基因技术在B细胞内表达免疫球蛋白后,也未能诱导B细胞的正常发育。

有意思的是,在没有Fnip1的初始B细胞,基本的信号分子仍能被正常激活,但是代谢调节因子AMPK及mTOR表现失调,在应答于代谢压力(初始B细胞受体交联及癌基因激活)时,导致了细胞过度生长,并增强细胞对凋亡的敏感性。

这些结果表明,卵巢滤泡激素相互作用蛋白1(Fnip1)对B细胞的发育及代谢平衡至关重要,表明Fnip1能够作为一个代谢检查点,保证初始B细胞具有足够的代谢能力来支持分裂,并限制由细胞过度生长造成的淋巴瘤的生成。(生物谷Deepblue编译)

Disruption of Fnip1 Reveals a Metabolic Checkpoint Controlling B Lymphocyte Development

Heon Park, Karen Staehling, Mark Tsang, Mark W. Appleby, Mary E. Brunkow, Daciana Margineantu, David M. Hockenbery, Tania Habib, H. Denny Liggitt, George Carlson, Brian M. Iritani.

The coordination of nutrient and energy availability with cell growth and division is essential for proper immune cell development and function.By using a chemical mutagenesis strategy in mice, we identified a pedigree that has a complete block in B cell development at the pre-B cell stage resulting from a deletion in the Fnip1 gene.Enforced expression of an immunoglobulin transgene failed to rescue B cell development. Whereas essential pre-B cell signaling molecules were activated normally in Fnip1-null pre-B cells, the metabolic regulators AMPK and mTOR were dysregulated, resulting in excessive cell growth and enhanced sensitivity to apoptosis in response to metabolic stress (pre-B cell receptor crosslinking, oncogene activation).These results indicate that Folliculin-interacting protein 1 (Fnip1) is vital for B cell development and metabolic homeostasis and reveal a metabolic checkpoint that may ensure that pre-B cells have sufficient metabolic capacity to support division, while limiting lymphomagenesis caused by deregulated growth.

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