Basophil activation by anti-double-stranded DNA IgE antibody enhances B
cell differentiation in systemic lupus erythematosus
Abstract
Objects Recently, the involvement of basophils and IgE-type
autoantibodies in the pathogenesis of systemic lupus erythematosus (SLE)
has been elucidated using mouse models; however, few studies have been
conducted in humans. In this study, the role of basophils and
anti-double-stranded DNA (dsDNA) IgE in SLE was examined using human
samples. Methods The correlation between disease activity and
serum levels of anti-dsDNA IgE in SLE was evaluated using enzyme-linked
immunosorbent assay. Cytokines produced by IgE-stimulated basophils from
healthy subjects were assessed using RNA sequences. The interaction of
basophils and B cells to promote B cell differentiation was investigated
using a co-culture system. The ability of basophils from patients with
SLE with anti-dsDNA IgE to create cytokines promoting B cell
differentiation in response to dsDNA was examined using real-time
polymerase chain reaction. Results Anti-dsDNA IgE levels in the
serum of patients with SLE correlated with disease activity. Healthy
donor basophils produced IL-3, IL-4, and TGF-β1 after anti-IgE
stimulation. Co-culture of B cells with anti-IgE-stimulated basophils
increased plasmablasts which were cancelled by neutralizing IL-4. After
encountering the antigen, basophils released IL-4 more quickly than
follicular helper T cells. Basophils isolated from patients with
anti-dsDNA IgE promoted IL-4 expression by adding dsDNA.
Conclusions These results suggest that basophils contribute to
the pathogenesis of SLE by promoting B cell differentiation via
dsDNA-specific IgE in patients similar to the process described in mouse
models.