Mathas Stephan, Janz Martin, Hummel Franziska, Hummel Michael, Wollert-Wulf Brigitte, Lusatis Simone, Anagnostopoulos Ioannis, Lietz Andreas, Sigvardsson Mikael, Jundt Franziska, Jöhrens Korinna, Bommert Kurt, Stein Harald, Dörken Bernd
Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany.
Nat Immunol. 2006 Feb;7(2):207-15. doi: 10.1038/ni1285. Epub 2005 Dec 20.
B cell differentiation is controlled by a complex network of lineage-restricted transcription factors. How perturbations to this network alter B cell fate remains poorly understood. Here we show that classical Hodgkin lymphoma tumor cells, which originate from mature B cells, have lost the B cell phenotype as a result of aberrant expression of transcriptional regulators. The B cell-specific transcription factor program was disrupted by overexpression of the helix-loop-helix proteins ABF-1 and Id2. Both factors antagonized the function of the B cell-determining transcription factor E2A. As a result, expression of genes specific to B cells was lost and expression of genes not normally associated with the B lineage was upregulated. These data demonstrate the plasticity of mature human lymphoid cells and offer an explanation for the unique classical Hodgkin lymphoma phenotype.
B细胞分化受一系列谱系限制性转录因子构成的复杂网络调控。该网络的扰动如何改变B细胞命运仍知之甚少。我们在此表明，源自成熟B细胞的经典霍奇金淋巴瘤肿瘤细胞，由于转录调节因子的异常表达而丧失了B细胞表型。B细胞特异性转录因子程序因螺旋-环-螺旋蛋白ABF-1和Id2的过表达而被破坏。这两种因子均拮抗B细胞决定性转录因子E2A的功能。结果，B细胞特异性基因的表达丧失，而通常与B谱系无关的基因表达上调。这些数据证明了成熟人类淋巴细胞的可塑性，并为独特的经典霍奇金淋巴瘤表型提供了解释。
