PMID- 21469111 OWN - NLM STAT- MEDLINE DCOM- 20110624 LR - 20211020 IS - 1521-4141 (Electronic) IS - 0014-2980 (Print) IS - 0014-2980 (Linking) VI - 41 IP - 5 DP - 2011 May TI - Translocation of an antibody transgene requires AID and occurs by interchromosomal switching to all switch regions except the mu switch region. PG - 1456-64 LID - 10.1002/eji.201041077 [doi] AB - Immunoglobulin (Ig) class switch recombination (CSR) occurs most often by intrachromosomal recombinations between switch (S) regions located on a single chromosome, but it can also occur by interchomosomal recombinations between Ig heavy chain (Igh) S regions located on chomosomal homologs. Interchromosomal recombinations have also been found between chromosomes that are not homologs; examples are Igh/c-myc and Igh/transgene translocations. Most, but not all, studies have indicated that activation-induced cytidine deaminase (AID) is important in Igh/c-myc translocations. The role of AID has not been determined for Igh/transgene translocations. We now show that the majority of Igh/transgene translocations between non-homologs from an Ig transgenic mouse are dependent on AID, but we also find a small number of these translocations that can occur in the absence of AID. Surprisingly, our results also indicate that, although Sgamma switch sequences in the endogenous Igh locus participate in chromosomal translocations with the non-homolog transgene-bearing chromosome, Smu switch sequences do not. This contrasts with the fact that both endogenous Smu and Sgamma sequences participate in intrachromosomal CSR. Our findings suggest the operation of a regulatory mechanism that can differentially control the accessibility of Smu and Sgamma regions for non-homolog translocations even when both are accessible for intrachromosomal recombination. CI - Copyright (c) 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Shansab, Maryam AU - Shansab M AD - Program in Immunology and Department of Pathology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA. FAU - Eccleston, Jennifer M AU - Eccleston JM FAU - Selsing, Erik AU - Selsing E LA - eng GR - R01 AI024465/AI/NIAID NIH HHS/United States GR - R01 AI024465-15/AI/NIAID NIH HHS/United States GR - AI24465/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110411 PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (Immunoglobulin Heavy Chains) RN - EC 3.5.4.- (AICDA (activation-induced cytidine deaminase)) RN - EC 3.5.4.5 (Cytidine Deaminase) SB - IM MH - Animals MH - Blotting, Southern MH - Cytidine Deaminase/deficiency/genetics/*metabolism MH - *Genes, Immunoglobulin Heavy Chain MH - Immunoglobulin Heavy Chains/genetics MH - Immunoglobulin Switch Region/*genetics MH - In Situ Hybridization, Fluorescence MH - Mice MH - Mice, Transgenic MH - Polymerase Chain Reaction MH - Recombination, Genetic MH - *Transgenes MH - *Translocation, Genetic PMC - PMC3142474 MID - NIHMS297859 COIS- Conflict of interest The authors have no financial conflict of interest. EDAT- 2011/04/07 06:00 MHDA- 2011/06/28 06:00 PMCR- 2012/05/01 CRDT- 2011/04/07 06:00 PHST- 2010/09/20 00:00 [received] PHST- 2011/01/20 00:00 [revised] PHST- 2011/02/09 00:00 [accepted] PHST- 2011/04/07 06:00 [entrez] PHST- 2011/04/07 06:00 [pubmed] PHST- 2011/06/28 06:00 [medline] PHST- 2012/05/01 00:00 [pmc-release] AID - 10.1002/eji.201041077 [doi] PST - ppublish SO - Eur J Immunol. 2011 May;41(5):1456-64. doi: 10.1002/eji.201041077. Epub 2011 Apr 11.