Mechanisms for the acquisition of somatic hypermutation activity during the late B cell development

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670239
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Tokyo University of Science
• Principal Investigator: Kitamura Daisuke 東京理科大学, 研究推進機構生命医科学研究所, 教授 (70204914)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 免疫学 / 体細胞突然変異 / 胚中心 / B細胞 / 抗体

Outline of Final Research Achievements

Activation-induced deaminase (AID) is essential for both somatic hypermutation (SHM) and class switch recombination (CSR), contributing to antibody affinity maturation. Although both occurs in germinal center (GC) B cells, only CSR is induced in B cells cultured with mitogen, expressing AID. Therefore some mechanism works in germinal center B cells to induce SHM but not in cultured B cells.
We utilized the system called iGB cell culture, in which naive B cells are cultured on feeder cells with IL-4 or IL-21. The cultured B cells greatly proliferate, acquire GC phenotype and undergo CSR, but not SHM. However, memory B cells cultured similarly with Ag stimulation undergo SHM. Blimp1-deficient B cells accumulated even more SHM. Introduction of Bcl6 enabled B cells to proliferate for more than 2 months with accumulating SHM, but eventually only clones with a dominant nuclear AID kept undergoing SHM.

Free Research Field

免疫学