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AID is essential for immunoglobulin V gene conversion in a cultured B cell line.

Abstract
Following productive V gene rearrangement, the functional immunoglobulin genes in the B lymphocytes of man and mouse are subjected to two further types of genetic modification. Class-switch recombination, a region-specific but largely nonhomologous recombination process, leads to a change in constant region of the expressed antibody. Somatic hypermutation introduces multiple single nucleotide substitutions in and around the rearranged V gene segments and underpins affinity maturation. However, in chicken and rabbits (but not man or mouse), an additional mechanism, gene conversion, is a major contributor to V gene diversification. It has been demonstrated recently that both switch recombination and hypermutation are ablated in mice and humans lacking AID, a B cell-specific protein of unknown molecular activity. Here we show that disruption of AID in the DT40 chicken B cell lymphoma leads to a failure to perform immunoglobulin V gene conversion. Thus, AID is required for all three immunoglobulin gene modification programs (gene conversion, hypermutation, and switch recombination) and acts in the initiation or execution of these processes rather than in bringing the B cell to an appropriate stage of differentiation.
AuthorsReuben S Harris, Julian E Sale, Svend K Petersen-Mahrt, Michael S Neuberger
JournalCurrent biology : CB (Curr Biol) Vol. 12 Issue 5 Pg. 435-8 (Mar 05 2002) ISSN: 0960-9822 [Print] England
PMID11882297 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Immunoglobulin Variable Region
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase
Topics
  • Amino Acid Sequence
  • Animals
  • B-Lymphocytes (enzymology, immunology)
  • Cell Line
  • Chickens
  • Cytidine Deaminase (deficiency, genetics)
  • Gene Conversion
  • Gene Targeting
  • Humans
  • Immunoglobulin Variable Region (genetics)
  • Mice
  • Molecular Sequence Data
  • Rabbits
  • Sequence Homology, Amino Acid

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