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首页> 外文期刊>Nature >Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling
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Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling

机译：慢性淋巴细胞性白血病由抗原独立的细胞自主信号传导驱动

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摘要

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.
机译：B细胞抗原受体（BCR）的表达是慢性淋巴细胞性白血病（CLL）的一个重要特征，CLL是西方国家最普遍的B细胞瘤形成之一。在不同的CLL患者中存在定型和准相同的BCR，这表明对特定抗原的识别可能会推动CLL的发病。在这里，我们表明，与其他B细胞瘤形成不同，CLL衍生的BCR诱导抗原独立的细胞自主信号传导，该信号依赖于BCR的重链互补决定区（HCDR3）和内部表位。确实，将CLL衍生的BCR的HCDR3转移给非自主活性BCR提供了自主的信号传导能力，而内部表位的突变则消除了这种能力。由于分泌的CLL衍生的BCR与靶细胞的结合需要BCR表达，而内部表位的突变降低了这种结合，因此我们的结果表明了CLL发病机制的新模型，细胞自主抗原独立信号传导是关键的致病性机制。

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  • 来源
    《Nature》 |2012年第7415期|p.309-312|共4页
  • 作者

    Marcus Duehren-von Minden; Rudolf UEbelhart; Dunja Schneider; Thomas Wossning; Martina P. Bach; Maike Buchner; Daniel Hofmann; Elena Surova; Marie Folio; Fabian Koehler; Hedda Wardemann; Katja Zirlik; Hendrik Veelken; Hassan Jumaa;

  • 作者单位

    Centre for Biological Signaling Studies (BIOSS), Albert-Ludwigs Universitat Freiburg, 79104 Freiburg, Germany;

    Centre for Biological Signaling Studies (BIOSS), Albert-Ludwigs Universitat Freiburg, 79104 Freiburg, Germany,Spemann Graduate School of Biology and Medicine, Albert-Ludwigs Universitat Freiburg, 79104 Freiburg, Germany;

    Centre for Biological Signaling Studies (BIOSS), Albert-Ludwigs Universitat Freiburg, 79104 Freiburg, Germany;

    Centre for Biological Signaling Studies (BIOSS), Albert-Ludwigs Universitat Freiburg, 79104 Freiburg, Germany;

    Centre for Biological Signaling Studies (BIOSS), Albert-Ludwigs Universitat Freiburg, 79104 Freiburg, Germany;

    Department of Hematology/Oncology, University Medical Center Freiburg, 79106 Freiburg, Germany;

    Centre for Biological Signaling Studies (BIOSS), Albert-Ludwigs Universitat Freiburg, 79104 Freiburg, Germany;

    Centre for Biological Signaling Studies (BIOSS), Albert-Ludwigs Universitat Freiburg, 79104 Freiburg, Germany,Spemann Graduate School of Biology and Medicine, Albert-Ludwigs Universitat Freiburg, 79104 Freiburg, Germany;

    Department of Hematology/Oncology, University Medical Center Freiburg, 79106 Freiburg, Germany;

    Centre for Biological Signaling Studies (BIOSS), Albert-Ludwigs Universitat Freiburg, 79104 Freiburg, Germany;

    Max Planck Research Group Molecular Immunology, Max Planck Institute for Infection Biology, 10117 Berlin, Germany;

    Department of Hematology/Oncology, University Medical Center Freiburg, 79106 Freiburg, Germany;

    Department of Hematology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands;

    Centre for Biological Signaling Studies (BIOSS), Albert-Ludwigs Universitat Freiburg, 79104 Freiburg, Germany,Department of Molecular Immunology, Faculty of Biology, Albert Ludwigs University of Freiburg and Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany;

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