近日,，來自華盛頓大學(xué)的研究人員表示,，他們發(fā)現(xiàn)了控制B淋巴細(xì)胞發(fā)育的一個代謝檢查點(diǎn)，即卵巢濾泡激素相互作用蛋白1(Fnip1),。相關(guān)研究成果于5月17日在線發(fā)表在Immunity上,。
協(xié)調(diào)好體內(nèi)代謝與細(xì)胞的生長及分裂之間的關(guān)系，對免疫細(xì)胞的正常發(fā)育及功能至關(guān)重要,。
最近,，Brian M. Iritani等人利用化學(xué)誘變方法，得到了一種特殊的小鼠品系,，他們發(fā)現(xiàn),，這種小鼠的B淋巴細(xì)胞在初始B細(xì)胞階段的發(fā)育受到阻礙，進(jìn)一步研究發(fā)現(xiàn),，這是因為該種小鼠缺失了Fnip1基因的緣故,。
然而，利用轉(zhuǎn)基因技術(shù)在B細(xì)胞內(nèi)表達(dá)免疫球蛋白后,，也未能誘導(dǎo)B細(xì)胞的正常發(fā)育,。
有意思的是，在沒有Fnip1的初始B細(xì)胞,，基本的信號分子仍能被正常激活,，但是代謝調(diào)節(jié)因子AMPK及mTOR表現(xiàn)失調(diào)，在應(yīng)答于代謝壓力（初始B細(xì)胞受體交聯(lián)及癌基因激活）時,，導(dǎo)致了細(xì)胞過度生長,，并增強(qiáng)細(xì)胞對凋亡的敏感性。
這些結(jié)果表明,，卵巢濾泡激素相互作用蛋白1(Fnip1)對B細(xì)胞的發(fā)育及代謝平衡至關(guān)重要,，表明Fnip1能夠作為一個代謝檢查點(diǎn),，保證初始B細(xì)胞具有足夠的代謝能力來支持分裂，并限制由細(xì)胞過度生長造成的淋巴瘤的生成,。（生物谷Deepblue編譯）
doi: 10.1016/j.immuni.2012.02.019
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PMID:
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.
