| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
CD40 plays an important role in B cell proliferation, survival, memory, and Ig class switch recombination (CSR). With the engagement of CD40 on B cells, IL-4 determines Ig CSR to epsilon and in particular, production of IgE that plays an important role in the pathogenesis of allergic diseases. On the other hand, B lymphocyte stimulator (BLyS) has been recently reported to have the ability to induce CD40-independent Ig CSR and plasmacytoid differentiation. We have found that a human Ig Fcγ-Fcε bifunctional chimeric protein (Ig Fcγ-Fcε) inhibited IL-4-induced CSR to epsilon in human B cells, Also, we have previously established a switch vector assay by using GFP as an indicator for substrate switch recombination (SSR) in human B cell line Ramos 2G6. In this study, the inhibitory effect of Ig Fcγ-Fcε on CD40-dependent IL-4-induced CSR was confirmed and quantified by employing this switch vector assay. At the same time, we examined the effect of Ig Fcγ-Fcε on BLyS-dependent IL-4-induced CSR. Ig Fcγ-Fcε inhibited both CD40-dependent and BLyS-dependent IL-4-induced SSR in a dose dependent manner, significantly reducing it at concentrations at or above 5 μg/ml.
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