title: Expression of AID transgene is regulated in activated B cells but not in resting B cells and kidney.
abstract: Activation-induced DNA cytidine deaminase (AID) is required for somatic hypermutation (SHM) and efficient class switch recombination (CSR) of immunoglobulin (Ig) genes. We created AID-transgenic mice that express AID ubiquitously under the control of a beta-actin promoter. When crossed with AID-/- mice, the AID-transgenic,AID-/- mice carried out SHM and CSR, showing that the AID transgenes were functional. However, the frequencies of SHM in V- and switch-regions, and CSR were reduced compared to those in a wild type AID background. Several criteria suggested that the inefficiency of SHM was due to reduced AID activity, rather than lack of recruiting error-prone DNA repair. High levels of AID mRNA were produced in resting B cells and kidney, cells that do not express AID in wild type mice. Compared with these cells, activated B cells expressed about an order of magnitude less AID mRNA suggesting that there may be a post-transcriptional mechanism that regulates AID mRNA levels in professional AID producers but not other cells. The AID protein expressed in resting B cells and kidney was phosphorylated at serine-38. Despite this modification, known to enhance AID activity, resting B cells did not undergo SHM. Apparently, the large amounts of AID in resting B cells are not targeted to Ig genes in vivo, in contrast to findings in vitro.
authors: Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
authors: Hong Ming
authors: HM
authors: Shen
authors: Grazyna
authors: G
authors: Bozek
authors: Carl A
authors: CA
authors: Pinkert
authors: Kevin
authors: K
authors: McBride
authors: Lili
authors: L
authors: Wang
authors: Amy
authors: A
authors: Kenter
authors: Ursula
authors: U
authors: Storb
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000201:enzymology*; D003564:Cytidine Deaminase / Q000235:genetics*; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007668:Kidney / Q000201:enzymology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D027041:Somatic Hypermutation, Immunoglobulin / Q000276:immunology; D019076:Transgenes; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D012694:Serine; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase