2012年8月14日 電 /生物谷BIOON/ --近日,，來自弗萊堡大學(xué)生物信號(hào)研究中心Hassan Jumaa教授領(lǐng)導(dǎo)的實(shí)驗(yàn)團(tuán)隊(duì)發(fā)現(xiàn)了一種促使免疫細(xì)胞轉(zhuǎn)變?yōu)閻盒园┘?xì)胞的分子機(jī)制。慢性淋巴細(xì)胞性白血?。–hronic Lymphocytic Leukaemia,，CLL)是西方國家常見的一種血癌,，患者機(jī)體細(xì)胞攜帶著致病轉(zhuǎn)化的關(guān)鍵因子，國際著名雜志Nature刊登了研究者的研究成果,，理解這些潛在的機(jī)制對(duì)于開發(fā)出減少疾病效應(yīng)的新型療法非常重要,。
健康人體內(nèi)含有許多成為B淋巴細(xì)胞的白細(xì)胞亞族，這些細(xì)胞主要負(fù)責(zé)產(chǎn)生對(duì)付感染的抗體,，B淋巴細(xì)胞特殊的受體分子可以利用“遙控車車鎖”的法則來檢測(cè)致病因子,，最終開始產(chǎn)生抗體。在CLL病人中,，這些受體的異常形式可以導(dǎo)致惡性B淋巴細(xì)胞的無限制增殖，最終免疫系統(tǒng)的健康細(xì)胞就會(huì)被抑制,。
到目前為止,，研究者們假設(shè)由病人機(jī)體產(chǎn)生的因子可以停靠在這種受體附近,，然后激活CLL病人的淋巴細(xì)胞,，研究者Jumaa說，在我們的研究中,，我們解釋了B淋巴細(xì)胞受體的特殊組分,，其負(fù)責(zé)CLL的產(chǎn)生和發(fā)展。在CLL病人的B淋巴細(xì)胞中,，受體組分FR2和HCDR3以某種特定形式產(chǎn)生,，隨后附近相同細(xì)胞的受體便會(huì)激活彼此來引發(fā)信號(hào)的級(jí)聯(lián)效應(yīng),，最終會(huì)促使癌細(xì)胞的無限分裂。
當(dāng)前,，以非特異性方式抑制疾病癥狀的化療方法應(yīng)用于CLL的治療中,，如今基于解碼CLL的基本分子機(jī)制，研究者開始著力于將他們理解的分子機(jī)制應(yīng)用于該疾病的治療中,，研究者表示,，在病人體內(nèi)控制多拷貝的FR2因子成為了可能，其隨后將靠近受體然后抑制附近受體互相結(jié)合,，這最終將降低級(jí)聯(lián)信號(hào),，抑制癌癥的發(fā)生。（生物谷Bioon.com）
編譯自：Researchers uncover how pathological cells activate themselves in chronic lymphocytic leukaemia
doi:10.1038/nature11309
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PMID:
Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling
Marcus Dühren-von Minden, Rudolf Übelhart, Dunja Schneider, Thomas Wossning, Martina P. Bach, Maike Buchner, Daniel Hofmann, Elena Surova, Marie Follo, Fabian Köhler, Hedda Wardemann, Katja Zirlik, Hendrik Veelken & Hassan Jumaa
B-cell antigen receptor (BCR) expression is an important feature of chronic lymphocytic leukaemia (CLL), one of the most prevalent B-cell neoplasias in Western countries1. The presence of stereotyped and quasi-identical BCRs in different CLL patients suggests that recognition of specific antigens might drive CLL pathogenesis. Here we show that, in contrast to other B-cell neoplasias, CLL-derived BCRs induce antigen-independent cell-autonomous signalling, which is dependent on the heavy-chain complementarity-determining region (HCDR3) and an internal epitope of the BCR. Indeed, transferring the HCDR3 of a CLL-derived BCR provides autonomous signalling capacity to a non-autonomously active BCR, whereas mutations in the internal epitope abolish this capacity. Because BCR expression was required for the binding of secreted CLL-derived BCRs to target cells, and mutations in the internal epitope reduced this binding, our results indicate a new model for CLL pathogenesis, with cell-autonomous antigen-independent signalling as a crucial pathogenic mechanism.
