Identification of co-factors specific for somatic hypermutation of immunoglobulin genes

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670150
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Nagahama Institute of Bio-Science and Technology
• Principal Investigator: REIKO Shinkura 長浜バイオ大学, バイオサイエンス学部, 教授 (50362471)
• Research Collaborator: YAMADA Keisuke 長浜バイオ大学, バイオサイエンス研究科
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 抗体 / 遺伝子組み換え / 体細胞突然変異

Outline of Final Research Achievements

Antigen stimulation induces antibody diversification through somatic hypermutation (SHM) and class switch recombination (CSR). SHM introduces point mutations at high frequency in the variable (V) region gene, whereas CSR is a region-specific recombination that replaces the heavy chain constant region (CH) gene from Cμ to other downstream CH gene, diversifying antibody effector function without changing their antigen specificity.
Activation-induced cytidine deaminase (AID) is essential for both SHM and CSR. However, it is unknown how AID regulates two genetic events, SHM and CSR. Previous studies showed that N-terminal mutant AIDs caused selective deficiency in SHM but retained CSR, suggesting the possibility that SHM activity of AID may require the SHM-specific cofactors interacting with N-terminal region of AID. In this study, we found several candidate molecules, which were co-immunoprecipitated with AID, but not G23S (a N-terminal mutant of AID), as SHM-specific cofactors.

Free Research Field

分子生物学、免疫学