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Urate crystals trigger B-cell receptor signal transduction and induce B-cell proliferation

  • Theodoros Eleftheriadis EMAIL logo , Georgios Pissas , Georgia Antoniadi , Georgios Filippidis , Vassilios Liakopoulos and Ioannis Stefanidis
Published/Copyright: January 13, 2020

Abstract

Background

Urate in its crystal form is a known danger-associated molecular pattern, which after its internalization activates cells of the innate immune system. However, by inducing lipid raft sequestration and clustering of membrane-bound proteins with immunoreceptor tyrosine-based activation motifs, urate crystals can also activate cells of the innate immune system without previous internalization. Also, urate crystals trigger T-cell receptor signal transduction and induce T-cell proliferation. In this study, we evaluated whether urate crystals can also initiate B-cell receptor (BCR) signal transduction and promote B-cell proliferation.

Methods

B cells were isolated from the blood of 10 individuals and cultured with or without urate at a concentration of 10 mg/dL, at which crystallization occurs. Phosphorylated Igα (CD79A) and c-Myc were assessed by Western blotting and B-cell proliferation with BrdU assay.

Results

Urate increased the level of phosphorylated Igα, a component of the BCR complex. Phosphorylation of Igα is the very proximal event in BCR signal transduction. Also, urate increased the expression of c-Myc, an essential transcription factor for BCR-induced B-cell proliferation. Finally, urate induces B-cell proliferation.

Conclusions

Urate crystals trigger BCR signal transduction and induce B-cell proliferation. The clinical significance of urate-induced B-cell activation remains to be elucidated.

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. T.E. designed the study, T.E. and G.P. performed the experiments, T.E., G.P., G.A., G.F., V.L., and I.S. analyzed the results, T.E. wrote the manuscript with help from G.P. I.S. supported all stages.

  3. Competing interests: The authors declare that they have no conflict of interests.

  4. Availability of data and materials: The analyzed datasets generated during the study are available from the corresponding author on reasonable request.

  5. Informed consent: Informed consent was obtained from each enrolled in the study.

  6. Ethical approval: The Ethics Committee of the Faculty of Medicine, University of Thessaly (Larissa, Greece), approved the study protocol (Number of approval: 558/10-2-2017).

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Received: 2019-02-18
Accepted: 2019-11-11
Published Online: 2020-01-13

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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