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

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Authors
Sim, Ji Hyun; Kim, Hang-Rae; Chang, Soog-Hee; Kim, In Je; Lipsky, Peter E.; Lee, Jisoo
Issue Date
2015-07-25
Publisher
BioMed Central
Citation
Arthritis Research & Therapy, 17(1):190
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.
Language
English
URI
http://hdl.handle.net/10371/109902
DOI
https://doi.org/10.1186/s13075-015-0687-1
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College of Medicine/School of Medicine (의과대학/대학원)Anatomy (해부학전공)Journal Papers (저널논문_해부학전공)
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