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

Title
Autoregulatory function of interleukin-10-producing pre-naïve B cells is defective in systemic lupus erythematosus
Authors
Sim J.H.Kim H.-R.Chang S.-H.Kim I.J.Lipsky P.E.Lee J.
Ewha Authors
이지수김인제
SCOPUS Author ID
이지수scopus; 김인제scopus
Issue Date
2015
Journal Title
Arthritis Research and Therapy
ISSN
1478-6354JCR Link
Citation
vol. 17, no. 1
Publisher
BioMed Central Ltd.
Indexed
SCI; SCIE; SCOPUS WOS scopus
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-aα) 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. © 2015 Sim et al.
DOI
10.1186/s13075-015-0687-1
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의학전문대학원 > 의학과 > Journal papers
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