时间：9月19日星期二10:30-12:00

Time：10:30 AM-12:00 PM，Tuesday, September 19，2023

主持人：西湖大学生命科学学院教授 俞晓春

    Host：Dr. Xiaochun Yu, Professor, School of Life Sciences

    地点：云谷校区E9-109

    Venue：E9-109, Yungu Campus

主讲嘉宾/Speaker:

Dr. Feilong Meng, PI, State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and CellBiology, Center for Excellence in Molecular Cell Science, Chinese Academy ofSciences; University of Chinese Academy of Sciences.

My research has focused on the mechanisms of antibody diversification in B lymphocytes, including antibody class switch and affinity maturation. Upon antigen stimulation, B cells can undergo cytidine deaminase AID-initiated antibody class switch recombination and somatic hypermutation processes to diversify the antigen receptor along with B cell clonal expansion. We aim to understand the molecular mechanisms underlying specific-targeting of cytidine deaminase AID, error-prone decoding of DNA lesions, and affinity-based selection of B cells. We also seek to establish new methods for antibody generation and discovery. In this course, we have uncovered genomic and epigenomic features of AID targeting at micrometer and nanometer scales, identified a critical regulator of orientation-specific DNA recombination, and invented a set of methods for ex vivo antibody affinity maturation and selection.

讲座摘要/Abstract:

Somatic hypermutation, initiated by activated-induced deaminase (AID), generates a diverse pool of mutations to allow antibody affinity maturation upon pathogen invasion. Why hypermutation is focused on the three nonconsecutive complementarity-determining-regions remains enigmatic. Here, we found that preferential mutagenesis is dependent on the mesoscale DNA sequence surrounding the AID-targeted cytidines. The in vivo hypermutation profile is mimicable in in vitro deaminase assays under physiological conditions. Mesoscale single-strand DNA sequence influences its binding to the charged-patch of AID, resulting in differential deaminase activity. We identified the short AID-attracting sequence and demonstrate their function in increasing mutability of an otherwise cold region. Our results show an unexpected non-coding role of antibody coding sequence in directing hypermutation and paved the way to the synthetic-design of antibody-humanized animal models.

联系人/Contact：

生命科学学院

于文越 yuwenyue@westlake.edu.cn