Grant: Operating Grant

Antibodies can recognize and eliminate any pathogen or toxin. Since pathogens are virtually infinite, antibodies need to adapt. To do this, almost every B lymphocyte modifies the genes that encode its antibody in two regions. One is the region that binds to the antigen. The other is the region that interacts with additional components of the immune system. Both modifications are fundamental for the immune response and are initiated by the enzyme named AID. AID shapes the antibody genes by making a lesion. The imprecise repair of this lesion by genome maintenance pathways is what changes the antibody genes. This is exactly the same way in which cancer starts and therefore this is a dangerous process and must be strictly regulated to minimize the risk of collateral damage. We study the coordination between AID and the mechanisms of repair. There are many repair pathways. Some make no mistakes; hence they cannot help the immune response. Others would make too much damage and increase the risk of cancer or immunodeficiency. We are studying how the initiation of damage by AID and the subsequent repair are synchronized, most likely by AID. This is a fundamental mechanism that can explain the basis of lymphomas and other cancers that are linked to AID activity, as well as immune diseases arising from too much or too little antibody gene diversification.