title: AID-driven deletion causes immunoglobulin heavy chain locus suicide recombination in B cells.
abstract: Remodeling of immunoglobulin genes by activation-induced deaminase (AID) is required for affinity maturation and class-switch recombination in mature B lymphocytes. In the immunoglobulin heavy chain locus, these processes are predominantly controlled by the 3' cis-regulatory region. We now show that this region is transcribed and undergoes AID-mediated mutation and recombination around phylogenetically conserved switchlike DNA repeats. Such recombination, which we term locus suicide recombination, deletes the whole constant region gene cluster and thus stops expression of the immunoglobulin of the B cell surface, which is critical for B cell survival. The frequency of this event is approaching that of class switching and makes it a potential regulator of B cell homeostasis.
authors.affiliation: Limoges University, CNRS, 2 rue Marcland, 87025 Limoges Cedex, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Péron
authors.forename: Brice
authors.initials: B
authors.lastname: Laffleur
authors.forename: Nicolas
authors.initials: N
authors.lastname: Denis-Lagache
authors.forename: Jeanne
authors.initials: J
authors.lastname: Cook-Moreau
authors.forename: Aurélien
authors.initials: A
authors.lastname: Tinguely
authors.forename: Laurent
authors.initials: L
authors.lastname: Delpy
authors.forename: Yves
authors.initials: Y
authors.lastname: Denizot
authors.forename: Eric
authors.initials: E
authors.lastname: Pinaud
authors.forename: Michel
authors.initials: M
authors.lastname: Cogné
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival; D003564:Cytidine Deaminase / Q000378:metabolism*; D017353:Gene Deletion; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D050438:Genes, Immunoglobulin Heavy Chain; D006706:Homeostasis; D006801:Humans; D017578:Immunoglobulin Class Switching; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase