title: AID from bony fish catalyzes class switch recombination.
abstract: Class switch recombination was the last of the lymphocyte-specific DNA modification reactions to appear in the evolution of the adaptive immune system. It is absent in cartilaginous and bony fish, and it is common to all tetrapods. Class switching is initiated by activation-induced cytidine deaminase (AID), an enzyme expressed in cartilaginous and bony fish that is also required for somatic hypermutation. Fish AID differs from orthologs found in tetrapods in several respects, including its catalytic domain and carboxy-terminal region, both of which are essential for the switching reaction. To determine whether evolution of class switch recombination required alterations in AID, we assayed AID from Japanese puffer and zebra fish for class-switching activity in mouse B cells. We find that fish AID catalyzes class switch recombination in mammalian B cells. Thus, AID had the potential to catalyze this reaction before the teleost and tetrapod lineages diverged, suggesting that the later appearance of a class-switching reaction was dependent on the evolution of switch regions and multiple constant regions in the IgH locus.
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Vasco M
authors.initials: VM
authors.lastname: Barreto
authors.forename: Qiang
authors.initials: Q
authors.lastname: Pan-Hammarstrom
authors.forename: Yaofeng
authors.initials: Y
authors.lastname: Zhao
authors.forename: Lennart
authors.initials: L
authors.lastname: Hammarstrom
authors.forename: Ziva
authors.initials: Z
authors.lastname: Misulovin
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002384:Catalysis; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000235:genetics / Q000502:physiology*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D023741:Takifugu; D015027:Zebrafish; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase