CCII Vice-Director Sidonia Fagarasan, Masamichi Muramatsu (FBRI, Kobe) et al. have recently published “Activation-induced cytidine deaminase: The missing piece of many puzzles” in the international scientific journal Cell. Written to commemorate the 25th anniversary of the first groundbreaking papers demonstrating the function of Activation-induced cytidine deaminase (AID), the review discusses Professor Honjo‘s quest to decipher the molecular basis of immunoglobulin diversity — a journey that for him began as a young postdoc in the 1970s. The discovery of the AID enzyme fundamentally changed our understanding of the vertebrate immune system.
Figure: Early experiments on AID expression and the design of the knockout vector
Pages from Muramatsu’s laboratory notebooks
The most significant achievement of the AID discovery was its proof that two complex biological phenomena— Somatic Hypermutation and Class Switch Recombination—which had long remained scientific mysteries are driven by the action of a single enzyme. This fundamentally overturned the expectations of immunologists, who considered the two processes distinct at the molecular level. Today, AID is known not only as the cornerstone of acquired immunity but also for its powerful DNA mutagenic activity, which links it deeply to the mechanism of cancer development, particularly in lymphomas.
The paper also details the importance of both human and model organism research, showing how the role of AID, a gene previously cloned in the Honjo lab, was deciphered by mechanistic work in mice combined with detailed analyses of patients with a rare immunodeficiency, described in a companion work by Anne Durandy, Alain Fischer and their colleagues at Necker Hospital, Paris.
In CCII Director Tasuku Honjo’s laboratory, research continues to be driven by the goal of overcoming intractable diseases such as cancer and autoimmune disorders. Elucidating the detailed mechanisms that control the “double-edged sword” of AID activity, as well as the diseases caused by its dysregulation, is an important part of their work, and of their colleagues at CCII.
Publication details
【Journal】Cell
【Title】Activation-induced cytidine deaminase: The missing piece of many puzzles
【Authors】Thiago Carvalho, Sidonia Fagarasan, Masamichi Muramatsu
【Date of publication】November 26, 2025（Online）