title: B cells facilitate platelet production mediated by cytokines in patients with essential thrombocythaemia.
abstract: 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.
authors.forename: C-C
authors.initials: CC
authors.lastname: Liu
authors.forename: S-C
authors.initials: SC
authors.lastname: Wang
authors.forename: C-W
authors.initials: CW
authors.lastname: Kao
authors.forename: R-K
authors.initials: RK
authors.lastname: Hsieh
authors.forename: M-C
authors.initials: MC
authors.lastname: Chang
authors.forename: Y-F
authors.initials: YF
authors.lastname: Chang
authors.forename: K-H
authors.initials: KH
authors.lastname: Lim
authors.affiliation: 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: cgchen@life.nthu.edu.tw.
authors.forename: C G
authors.initials: CG
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019138:Antibodies, Blocking / Q000494:pharmacology; D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D001792:Blood Platelets / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D013920:Thrombocythemia, Essential / Q000235:genetics / Q000276:immunology*; D034061:Thrombopoiesis / Q000187:drug effects / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D019138:Antibodies, Blocking; D053264:B-Cell Activating Factor; D007375:Interleukin-1; D015850:Interleukin-6; D051197:Toll-Like Receptor 4; D053614:Janus Kinase 2
keywords: B cell-activating factor; Essential thrombocythaemia; IL-1beta; IL-6; TLR4