Liu C-C, Wang S-C, Kao C-W, Hsieh R-K, Chang M-C, Chang Y-F, Lim K-H, Chen C G
Caleb Chen, MD, Department of Haematology, Mackay Memorial Hospital, 92 Zhong-Shen N. Road Sec. 2, Taipei 10449, Taiwan, Tel.: +886 2 2543 3535, Fax: +886 2 2511 8424, E-mail:
Thromb Haemost. 2014 Sep 2;112(3):537-50. doi: 10.1160/TH13-11-0949. Epub 2014 Jun 5.
We investigated the role of activated B cells in thrombopoiesis through the production of interleukin (IL)-1beta and IL-6 in patients with essential thrombocythaemia. The number of B cells did not differ between essential thrombocythaemia patients, irrespective of the presence of Janus activated kinase-2 V617F mutation or wild type, and age-matched healthy adults. However, the number of IL-1beta/IL-6-producing B cells was significantly higher in essential thrombocythaemia patients than that in healthy controls. The relatively high level of IL-1beta/IL-6 production by B cells was associated with serum B cell-activating factor and expression of Toll-like receptor 4 on B cells. A high level of B cell-activating factor was present in essential thrombocythaemia patients with both Janus activated kinase-2 genotypes. Incubation with B cell-activating factor enhanced the expression of Toll-like receptor 4 on B cells. IL-1beta and IL-6 production was not stimulated by B cell-activating factor alone; Toll-like receptor 4 was activated by lipopolysaccharide or patients' sera to produce IL-1beta and IL-6 in B cells. Moreover, essential thrombocythaemia patient B cells facilitated megakaryocyte differentiation when co-cultured with CD34+ haematopoietic stem cells. Antibody neutralisation of IL-1beta and IL-6 attenuated megakaryocyte differentiation. These data suggest that B cells play a crucial role in thrombopoiesis in essential thrombocythaemia patients.
我们通过研究原发性血小板增多症患者中活化B细胞产生白细胞介素（IL）-1β和IL-6的情况，来探究其在血小板生成中的作用。无论是否存在Janus活化激酶-2 V617F突变或野生型，原发性血小板增多症患者与年龄匹配的健康成年人相比，B细胞数量并无差异。然而，原发性血小板增多症患者中产生IL-1β/IL-6的B细胞数量显著高于健康对照组。B细胞产生的IL-1β/IL-6水平相对较高，与血清B细胞活化因子以及B细胞上Toll样受体4的表达有关。在具有两种Janus活化激酶-2基因型的原发性血小板增多症患者中均存在高水平的B细胞活化因子。用B细胞活化因子孵育可增强B细胞上Toll样受体4的表达。单独的B细胞活化因子不会刺激IL-1β和IL-6的产生；Toll样受体4可被脂多糖或患者血清激活，从而在B细胞中产生IL-1β和IL-6。此外，当与CD34 +造血干细胞共培养时，原发性血小板增多症患者的B细胞可促进巨核细胞分化。对IL-1β和IL-6进行抗体中和可减弱巨核细胞分化。这些数据表明，B细胞在原发性血小板增多症患者的血小板生成中起关键作用。
