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B cells facilitate platelet production mediated by cytokines in patients with essential thrombocythaemia

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: https://doi.org/10.1160/TH13-11-0949
Issue: 2014: 112/3 (Sep) pp. 427–626
Pages: 537-550

B cells facilitate platelet production mediated by cytokines in patients with essential thrombocythaemia

Online Supplementary Material

C.-C. Liu (1, 2), S.-C. Wang (3), C.-W. Kao (4), R.-K. Hsieh (4), M.-C. Chang (4, 5), Y.-F. Chang (4), K.-H. Lim (4), C. G. Chen (3, 4)

(1) Department of Medical Technology, Yuanpei University of Science and Technology, Hsin-Chu, Taiwan; (2) Health Evaluation Centre, Mackay Memorial Hospital, Taipei, Taiwan; (3) Institute of Molecular Medicine, National Tsing-Hua University, Hsin-Chu, Taiwan; (4) Department of Haematology, GCRC Laboratory, Mackay Memorial Hospital, Taipei, Taiwan; (5) Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan

Keywords

essential thrombocythaemia, B cell-activating factor, TLR4, IL-1beta, IL-6

Summary

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.

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