圖片說(shuō)明：人體能確定B細(xì)胞的最優(yōu)數(shù)量（綠色為B細(xì)胞受體,，橙色圓柱體為BlyS）,。
（圖片來(lái)源：Michael P. Cancro, Ph.D., University of Pennsylvania School of Medicine）
美國(guó)科學(xué)家近日通過(guò)研究,，闡明了人體如何確定血液中是否存在足夠的成熟B細(xì)胞,，以產(chǎn)生抗體抵御細(xì)菌感染,。這一發(fā)現(xiàn)對(duì)于移植醫(yī)學(xué)和自身免疫性疾病的治療具有重要意義,。相關(guān)論文11月2日在線發(fā)表于《自然—免疫學(xué)》（Nature Immunology）,。
美國(guó)賓夕法尼亞大學(xué)醫(yī)學(xué)院的Michael P. Cancro和同事發(fā)現(xiàn)，一種名為BlyS的蛋白綁定到B細(xì)胞表面的受體上,，當(dāng)循環(huán)中的BlyS越多,，成熟B細(xì)胞就越多。通過(guò)向免疫系統(tǒng)中添加BlyS,，調(diào)控成熟B細(xì)胞生成數(shù)量的“剎車”就會(huì)變松弛,。另一方面，人體還能通過(guò)這一平衡中的其它受體阻止B細(xì)胞的存活,，借以預(yù)防狼瘡等自身免疫性疾病,。
Cancro說(shuō)：“人體中含有穩(wěn)定數(shù)量的B細(xì)胞被認(rèn)為是正常的。我們發(fā)現(xiàn),，B細(xì)胞表面上的兩種受體間的分子交談（crosstalk）平衡了某種需要——存在足夠的B細(xì)胞以實(shí)現(xiàn)有益的免疫響應(yīng),，同時(shí)預(yù)防自身免疫性。”
這一研究揭示了這兩種受體間復(fù)雜的相互影響,。這使得它們能夠整合信號(hào),，但卻彼此矛盾。研究人員說(shuō)：“一個(gè)受體向細(xì)胞核發(fā)送信號(hào)說(shuō),，‘是的,，保持存活,，身體需要更多的B細(xì)胞’；而另一個(gè)說(shuō),，‘等等,，小心哪些B細(xì)胞應(yīng)該存活’。”
另外,，研究人員還發(fā)現(xiàn),，如果BlyS受到抑制，大多數(shù)B細(xì)胞都會(huì)死亡,。但是有些B細(xì)胞仍然存活,，這些B細(xì)胞負(fù)責(zé)記憶人體接種過(guò)什么以及遭受了什么樣的感染風(fēng)險(xiǎn)。
研究人員表示,，這些發(fā)現(xiàn)最終將導(dǎo)致一種醫(yī)學(xué)干預(yù),，即在自身免疫性疾病的預(yù)防、診斷及治療中調(diào)節(jié)B細(xì)胞的行為,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Immunology,，doi:10.1038/ni.1666，Jason E Stadanlick,，Michael P Cancro
Tonic B cell antigen receptor signals supply an NF-κB substrate for prosurvival BLyS signaling
Jason E Stadanlick1, Mary Kaileh2, Fredrick G Karnell1, Jean L Scholz1, Juli P Miller1, William J Quinn III1, Randall J Brezski1, Laura S Treml1, Kimberly A Jordan3, John G Monroe1, Ranjan Sen2 & Michael P Cancro1
Abstract
The survival of transitional and mature B cells requires both the B cell antigen receptor (BCR) and BLyS receptor 3 (BR3), which suggests that these receptors send signals that are nonredundant or that engage in crosstalk with each other. Here we show that BCR signaling induced production of the nonclassical transcription factor NF-κB pathway substrate p100, which is required for transmission of BR3 signals and thus B cell survival. The capacity for sustained p100 production emerged during transitional B cell differentiation, the stage at which BCR signals begin to mediate survival rather than negative selection. Our findings identify a molecular mechanism for the reliance of primary B cells on continuous BR3 and BCR signaling, as well as for the gradual resistance to negative selection that is acquired during B cell maturation.
1 Deparment of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
2 Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
3 Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania 19104, USA.
