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.
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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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