2004 Fiscal Year Final Research Report Summary
Inhibition of IgE-production by Ig Fcγ-Fcε chimeric protein
| Project/Area Number |
15591803
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Otorhinolaryngology
|
|---|
| Research Institution | University of Fukui (2004)
福井医科大学 (2003) |
|---|
Principal Investigator |
YAMADA Takechiyo University of Fukui Hospital, Lecturer, 医学部附属病院, 講師 (70283182)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Keywords | IgE / chimeric protein / closs switch recombination / B cell / allergy |
|---|
| 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.
|
