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Thromb Haemost 2014; 112(03): 537-550
DOI: 10.1160/TH13-11-0949
Platelets and Blood Cells
Schattauer GmbH

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

Chuan-Chuan Liu
1   Health Evaluation Centre, Mackay Memorial Hospital, Taipei, Taiwan
2   Department of Medical Technology, Yuanpei University of Science and Technology, Hsin-Chu, Taiwan
,
Shu-Ching Wang
5   Institute of Molecular Medicine, National Tsing-Hua University, Hsin-Chu, Taiwan
,
Chen-Wei Kao
3   Department of Haematology, GCRC Laboratory, Mackay Memorial Hospital, Taipei, Taiwan
,
Ruey-Kuen Hsieh
3   Department of Haematology, GCRC Laboratory, Mackay Memorial Hospital, Taipei, Taiwan
,
Ming-Chih Chang
3   Department of Haematology, GCRC Laboratory, Mackay Memorial Hospital, Taipei, Taiwan
4   Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan
,
Yi-Fang Chang
3   Department of Haematology, GCRC Laboratory, Mackay Memorial Hospital, Taipei, Taiwan
,
Ken-Hong Lim
3   Department of Haematology, GCRC Laboratory, Mackay Memorial Hospital, Taipei, Taiwan
,
Caleb Gonshen Chen
3   Department of Haematology, GCRC Laboratory, Mackay Memorial Hospital, Taipei, Taiwan
5   Institute of Molecular Medicine, National Tsing-Hua University, Hsin-Chu, Taiwan
› Author Affiliations Financial support: This work was supported by Mackay Memorial Hospital grants.
Further Information

Publication History

Received: 18 November 2013

Accepted after major revision: 22 March 2014

Publication Date:
20 November 2017 (online)

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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.

Keywords

Essential thrombocythaemia - B cell-activating factor - TLR4 - IL-1beta - IL-6

 

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