hIgDFc-Ig inhibits B cell functions by regulating BCR-Lyn-Syk-NF-κB
signaling pathway in treatment for mice with collagen-induced arthritis
Abstract
Background and purpose: To investigate the effect of hIgDFc-Ig (DG), a
new biological agent that competitively binds to IgD receptors, on
collagen-induced arthritis and its potential mechanism in regulating B
cell antigen-receptor signaling pathway. Experimental approach: DBA1
mice were used to establish collagen-induced arthritis model, three
doses of DG were administered by intraperitoneal injection. Clinical
assessment of CIA, histopathological examination, flow cytometry,
western blotting, immunofluorescence staining, protein chips and other
methods were used to evaluate the therapeutic effects. The effects of DG
on Daudi cells and IgαIgβ KO Ramos cells stimulated by IgD were also
evaluated. Key results: We found that DG has a significant therapeutic
effect on CIA mice. DG relieved the clinical assessment of CIA mice and
improved the pathology of joints and spleen. In addition, DG can also
regulate B cell subsets in the PBMC and spleen of CIA mice, and decrease
the level of immunoglobulins. DG can inhibit the BCR signaling
activation stimulated by IgD and effect the expression of transcription
factors in vitro. In Ramos cells, Igβ or IgαIgβ knockout may reverse the
activation of BCR signal pathway under the stimulation of IgD.
Conclusion and Implications: DG may play a therapeutic role in CIA mice
by regulating BCR-Lyn-Syk-NF-κB signaling pathway, and may be a new
promising biological agent for rheumatoid arthritis.