This application requests support for a Keystone Symposia meeting entitled Mutations, Malignancy and Memory - Antibodies and Immunity, organized by F. Nina Papavasiliou and Sebastian D. Fugmann, which will be held in Boston, Massachusetts from March 18 - 22, 2012. Mutations in the human genome are regarded as potentially disastrous events that lead to carcinogenesis. From the vantage point of B cell immunology, however, programmed DNA alterations at the antibody gene loci are essential for efficient antibody responses. A plethora of recent findings are beginning to illuminate open questions about the precise molecular mechanisms of these diversification processes, their regulation, and how errors in these pathways lead to cancer. Furthermore, the very same class of mutator enzymes plays an underappreciated role in non- lymphoid cancers, in antiviral responses, and in epigenetic reprogramming. Lastly, antibody diversification not only shapes the repertoires of the immunological memory, but also those of auto-antibodies. The Keystone Symposia meeting on Mutations, Malignancy and Memory - Antibodies and Immunity will provide both a platform to integrate these more or less isolated fields, and an opportunity to identify interfaces that could be relevant for therapeutic approaches in malignancies and autoimmune diseases.
The human body can generate millions of different antibodies, against a wide array of targets, using a relatively small number of genes. Antibody-producing cells achieve this by mixing and matching (i.e., recombining) genes, and fragments of these genes, and by highly specific generation of mutations in the resulting recombined antibody genes. Though it is well understood that this process, when deregulated, can give rise to lymphomas - malignant tumors that arise in the lymph nodes or in other lymphoid tissue - it has recently become clear that the class of enzymes catalyzing genomic mutation (the cytidine deaminases) are also involved in genomic and transcriptomic reprogramming processes that underlie both specific developmental pathways as well as carcinogenesis. The Keystone Symposia meeting on Mutations, Malignancy and Memory - Antibodies and Immunity aims to gather several related scientific communities that do not often intermingle in order to critically discuss therapeutic approaches in malignancies and autoimmune diseases.