hIgDFc-Ig inhibit B cell functions by regulating BCR-Lyn-Syk-NF-κB
signaling pathway in treatment for mice with collagen-induced arthritis
Abstract
Abstract Background and purpose: To investigate the effect of hIgDFc-Ig
(DG), a new biological agent targets competition for binding 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 DG were administered by intraperitoneal injection.
Clinical assessment of CIA, histopathological examination, flow
cytometry, western blotting, immunofluorescence staining, protein chips
and so on were used to evaluated therapeutic effects. The competitive
effects on BCR-NF-κB signaling pathway were also evaluated in Daudi cell
lines in vitro. Key results: We found that DG has a obvious therapeutic
effect on CIA mice. DG relieved the clinical assessment of CIA mice and
improved the pathology of joints and spleen. In addition, regulated B
cell subsets in the PBMC and spleen of CIA mice, and decreased level of
immunoglobulins. DG can inhibit the over-activation of BCR signal by
increasing p-Lyn level, Co-treatment with DG (0.1-10 μg·ml-1)
dose-dependently down-regulated the BCR signaling and decreased the
iteraction between Syk and Btk stimulated by IgD in Daudi cell.
Conclusion and Implications: DG may play a therapeutic role in CIA mice
by regulating BCR-Lyn-Syk-NF-KB signaling pathway, and may be a new
promising biological agent for rheumatoid arthritis. Key words:
hIgDFc-Ig; B cell antigen receptor; Collagen-induced arthritis; NF-κB
signaling pathway