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About the Authors:
Philipp C. Rommel
Affiliation: Laboratory of Molecular Immunology, the Rockefeller University, New York, New York, United States of America
David Bosque
Affiliation: Laboratory of Molecular Immunology, the Rockefeller University, New York, New York, United States of America
Alexander D. Gitlin
Affiliation: Laboratory of Molecular Immunology, the Rockefeller University, New York, New York, United States of America
Gist F. Croft
Affiliation: Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, New York, New York, United States of America
Nathaniel Heintz
Affiliations Laboratory of Molecular Biology, The Rockefeller University, New York, New York, United States of America, Howard Hughes Medical Institute, The Rockefeller University, New York, New York, United States of America
Rafael Casellas
Affiliation: Genomics and Immunity, NIAMS, and Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland, United States of America
Michel C. Nussenzweig
Affiliations Laboratory of Molecular Immunology, the Rockefeller University, New York, New York, United States of America, Howard Hughes Medical Institute, The Rockefeller University, New York, New York, United States of America
Skirmantas Kriaucionis
Affiliations Laboratory of Molecular Biology, The Rockefeller University, New York, New York, United States of America, Ludwig Institute for Cancer Research and University of Oxford, Oxford, United Kingdom
Davide F. Robbiani
* E-mail: [email protected]
Affiliation: Laboratory of Molecular Immunology, the Rockefeller University, New York, New York, United States of America
Introduction
Activation-induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) and class switch recombination (CSR), two DNA diversification reactions of mature B lymphocytes. Upon activation in response to antigen, B cells proliferate, form germinal centers (specialized anatomical structures within lymphoid organs), and express high levels of AID [1]. At antibody (immunoglobulin) genes, AID deaminates cytosines into uracils on single-stranded DNA during transcription. The resulting uracil-guanine mismatch can be processed in many ways, leading to DNA mutations (SHM) and DNA double-strand breaks (an obligate intermediate during CSR). As a result, antibodies are generated with higher affinity against the antigen, and with distinct effector functions, such as the ability to bind specific leukocyte subsets or to be secreted across the mucosa [2–4]. In addition to its high but transient expression in B cells during the germinal center reaction, low but biologically active amounts of AID have been detected in developing B cells, although the significance...