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2015 ; 17
(1
): 190
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Autoregulatory function of interleukin-10-producing pre-naïve B cells is
defective in systemic lupus erythematosus
#MMPMID26209442
Sim JH
; Kim HR
; Chang SH
; Kim IJ
; Lipsky PE
; Lee J
Arthritis Res Ther
2015[Jul]; 17
(1
): 190
PMID26209442
show ga
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-?) 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.