Amplification of IL-21 signalling pathway through Bruton's tyrosine kinase in human B cell activation

Rheumatology
Sheau-Pey WangYoshiya Tanaka

Abstract

B cells play an important role in the pathogenesis of autoimmune diseases. The role of Bruton's tyrosine kinase (Btk) in cytokine-induced human B cell differentiation and class-switch recombination remains incompletely defined. This study analysed the effect of Btk on human activated B cells. Purified B cells from healthy subjects were stimulated with B cell receptor (BCR) and other stimuli with or without a Btk inhibitor and gene expression was measured. The B cell line BJAB was used to assess Btk-associated signalling cascades. Phosphorylated Btk (p-Btk) in peripheral blood B cells obtained from 10 healthy subjects and 41 patients with RA was measured by flow cytometry and compared with patient backgrounds. IL-21 signalling, in concert with BCR, CD40 and BAFF signals, led to robust expression of differentiation- and class-switch DNA recombination-related genes and IgG production in human B cells, all of which were significantly suppressed by the Btk inhibitor. Although phosphorylation of STAT1 and STAT3 was induced by co-stimulation with IL-21, BCR and CD40, STAT1 phosphorylation in the nucleus, but not in the cytoplasm, was exclusively impaired by Btk blockade. High levels of p-Btk were noted in B cells of RA patients compar...Continue Reading

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Citations

Feb 20, 2016·Chemico-biological Interactions·Yonghwang Ha, Hyun-Kyung Choi
Jan 5, 2016·Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology·Hiroaki Niiro
Jan 5, 2016·Nihon Rinshō Men'eki Gakkai kaishi = Japanese journal of clinical immunology·Shigeru Iwata, Yoshiya Tanaka
Mar 5, 2016·The Korean Journal of Internal Medicine·Yoshiya Tanaka
Sep 1, 2016·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Shingo NakayamadaYoshiya Tanaka
Oct 4, 2016·Expert Opinion on Pharmacotherapy·Shingo NakayamadaYoshiya Tanaka
Dec 29, 2016·Clinical and Experimental Medicine·Natália Aydos MarcondesGustavo Adolpho Moreira Faulhaber
Sep 30, 2017·Cytometry. Part B, Clinical Cytometry·Natália Aydos MarcondesGustavo Adolpho Moreira Faulhaber
Aug 24, 2017·Journal of Cellular Physiology·Palani Dinesh, Mahaboobkhan Rasool
Jun 26, 2020·ImmunoTargets and Therapy·Ana Lorenzo-VizcayaDavid A Isenberg
May 31, 2020·Joint, Bone, Spine : Revue Du Rhumatisme·Hsien-Tzung LiaoChia-Li Yu
Jun 26, 2021·Frontiers in Immunology·Wenhan DuLiwei Lu
Jun 22, 2021·Frontiers in Cell and Developmental Biology·Stefan F H NeysOdilia B J Corneth

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