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Cutting edge: circulating plasmablasts induce the differentiation of human T follicular helper cells via IL-6 production

Chavele, KM; Merry, E; Ehrenstein, MR; (2015) Cutting edge: circulating plasmablasts induce the differentiation of human T follicular helper cells via IL-6 production. The Journal of Immunology , 194 (6) pp. 2482-2485. 10.4049/jimmunol.1401190. Green open access

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Abstract

B cells require CD4(+) T follicular helper (Tfh) cells to progress through the germinal center and provide protective Ab responses. In this article, we reveal a reciprocal interaction whereby circulating human plasmablasts are potent inducers of the Tfh cell-differentiation program, including the expression of their key transcription factor Bcl-6. The markedly increased propensity of plasmablasts, compared with naive B cells, to induce Tfh cell differentiation was due to their increased production of IL-6. Specific targeting of IL-6 using tocilizumab therapy in patients with rheumatoid arthritis led to a significant reduction in circulating Tfh cell numbers and IL-21 production, which was correlated with reduced plasmablast formation. Our data uncover a positive-feedback loop between circulating plasmablasts and Tfh cells that could sustain autoimmunity and spread Ab-driven inflammation to unaffected sites; this represents an important therapeutic target, as well as reveals a novel mechanism of action for tocilizumab.

Type: Article
Title: Cutting edge: circulating plasmablasts induce the differentiation of human T follicular helper cells via IL-6 production
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.4049/jimmunol.1401190
Publisher version: http://dx.doi.org/10.4049/jimmunol.1401190
Language: English
Additional information: Copyright © 2015 The Authors This is an open-access article distributed under the terms of the CC-BY 3.0 Unported license (http://creativecommons.org/licenses/by/3.0/).
Keywords: Antibodies, Monoclonal, Humanized, Antigens, CD19, Arthritis, Rheumatoid, B-Lymphocytes, CD4-Positive T-Lymphocytes, Cell Differentiation, Cell Proliferation, Cells, Cultured, Coculture Techniques, DNA-Binding Proteins, Flow Cytometry, Humans, Inducible T-Cell Co-Stimulator Protein, Interleukin-6, Interleukins, Plasma Cells, Receptors, CXCR5, T-Lymphocytes, Helper-Inducer
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/1470820
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