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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2015

Open Access 01-12-2015 | Research article

Autoregulatory function of interleukin-10-producing pre-naïve B cells is defective in systemic lupus erythematosus

Authors: Ji Hyun Sim, Hang-Rae Kim, Soog-Hee Chang, In Je Kim, Peter E. Lipsky, Jisoo Lee

Published in: Arthritis Research & Therapy | Issue 1/2015

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Abstract

Introduction

Pre-naïve B cells represent an intermediate stage in human B-cell development with some functions of mature cells, but their involvement in immune responses is unknown. The aim of this study was to determine the functional role of normal pre-naïve B cells during immune responses and possible abnormalities in systemic lupus erythematosus (SLE) that might contribute to disease pathogenesis.

Methods

Pre-naïve, naïve, and memory B cells from healthy individuals and SLE patients were stimulated through CD40 and were analyzed for interleukin-10 (IL-10) production and co-stimulatory molecule expression and their regulation of T-cell activation. Autoreactivity of antibodies produced by pre-naïve B cells was tested by measuring immunoglobulin M (IgM) autoantibodies in culture supernatants after differentiation.

Results

CD40-stimulated pre-naïve B cells produce larger amounts of IL-10 but did not suppress CD4+ T-cell cytokine production. Activated pre-naïve B cells demonstrated IL-10-mediated ineffective promotion of CD4+ T-cell proliferation and induction of CD4+FoxP3+ T cells and IL-10 independent impairment of co-stimulatory molecule expression and tumor necrosis factor-alpha (TNF-α) and IL-6 production. IgM antibodies produced by differentiated pre-naïve B cells were reactive to single-stranded deoxyribonucleic acid. SLE pre-naïve B cells were defective in producing IL-10, and co-stimulatory molecule expression was enhanced, resulting in promotion of robust CD4+ T-cell proliferation.

Conclusions

There is an inherent and IL-10-mediated mechanism that limits the capacity of normal pre-naïve B cells from participating in cellular immune response, but these cells can differentiate into autoantibody-secreting plasma cells. In SLE, defects in IL-10 secretion permit pre-naïve B cells to promote CD4+ T-cell activation and may thereby enhance the development of autoimmunity.
Appendix
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Metadata
Title
Autoregulatory function of interleukin-10-producing pre-naïve B cells is defective in systemic lupus erythematosus
Authors
Ji Hyun Sim
Hang-Rae Kim
Soog-Hee Chang
In Je Kim
Peter E. Lipsky
Jisoo Lee
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2015
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-015-0687-1

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