Diversification des anticorps dans le centre germinatif par désamination de l'ADN et génération de l'uracile genomique chez les vertébrés

 

Javier Marcelo Di Noia

Institut de recherches cliniques de Montréal [IRCM]

 

Domaine : maladies infectieuses et immunitaires

Programme Chercheurs-boursiers - Senior

Concours 2018-2019

The ability of the immune system of humans and other vertebrates to defend itself from pathogens depends on its capacity to produce specific antibodies of high affinity and with functions tailored to each individual pathogen. This capacity is mediated by mechanisms that change (mutate) the antibody genes. Importantly, the same mechanisms that improve the antibodies can sometimes fail, causing immunodeficiency, or malfunction and predispose to hematological cancer. This is an inevitable trade-off of the way our sophisticated and highly effective immune system evolved, but it has real impact on human health in the present time. To pinpoint the possible causes of and remedies for these diseases, we must understand the normal functioning of these mechanisms. T

he major area of our research program studies the function and regulation of the enzyme that mutates the antibody genes, named AID, to understand how it works at the antibody genes and what limits its deleterious activity at other parts of the genome. We also study how the mutagenic mechanisms that change the antibody genes influence the biology of the B lymphocytes, the cells that produce antibodies, immediately after immunization or infection. Our research in this area has direct implication for human disease and vaccination strategies. The second area of our research program studies a recently discovered enzyme belonging to the same family of AID, which is likely to participate in the metabolism of the building blocks of DNA. This metabolism is limiting for cell proliferation and has implications in cancer, the metabolism of certain anticancer drugs, and the efficiency of viral infections.