AID for acquired immunity: understanding antibody memory

Antibody memory allows people to develop acquired immunity and is critical for vaccinations to be effective. There are two different hypotheses for the process behind antibody memory but so far both have been lacking evidence of crucial aspects of the proposed mechanisms. A collaboration of researchers at Kyoto University and Kanazawa University in Japan, have confirmed the activity of an enzyme called activation-induced cytidine deaminase (AID) that may provide the missing link.

Immunity is brought about by antibodies or immunoglubolins, present in the blood. These molecules take on millions of slightly differing structures for recognising different antigens, small structural units on viruses and bacteria. Antibody memory is based on the diversification of immunoglobulin genes, where DNA cleavage triggers processes that lead to generation of improved antibody.

Tasuku Honjo, Masamichi Muramatsu and their colleagues studied the behaviour of AID and hepatitius B virus in vitro. They transfected a type of human liver cell line with a small DNA molecule of the virus. Hypermutated DNA melts at a lower temperature, which allowed them to identify that hypermutation was taking place. They also sequenced cloned samples of DNA from AID expressing cells and compared them with green fluorescent protein expressing controls. They found 15 G-to-A and 10 C-to-T mutations, compared with only one G-to-A mutation in the controls. Further investigations confirmed that the C-to-T mutations resulted from RNA deamination.

“These results indicate that AID can deaminate both the viral RNA and DNA of hepatitis B virus,” explained by the authors. The results explain how AID interacts with viral RNA and help towards a better understanding of the processes behind acquired immunity.

Publication and Affiliation
Guoxin Liang^1,2, Kouichi Kitamura², Zhe Wang², Guangyan Liu², Sajeda Chowdhury², Weixin Fu^2,3, Miki Koura², Kousho Wakae², Tasuku Honjo*¹, and Masamichi Muramatsu*². RNA editing of hepatitis B virus transcripts by activation-induced cytidine deaminase. PNAS doi: 10.1073/pnas.1221921110(2013). Link

^1. Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
^2. Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan
^3. Center of Laboratory Technology and Experimental Medicine, China Medical University, Shenyang 11000, China

*corresponding author, e-mail address: honjo@mfour.med.kyoto-u.ac.jp or muramatu@med.kanazawa-u.ac.jp

ID: 201302H021