Translocation of an antibody transgene requires AID and occurs by interchromosomal switching to all switch regions except the mu switch region

• Published in: European journal of immunology Vol. 41; no. 5; pp. 1456 - 1464
• Main Authors: Shansab, Maryam, Eccleston, Jennifer M., Selsing, Erik
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01-05-2011; Wiley Subscription Services, Inc
• Subjects: Animals; B cells; Blotting, Southern; Cytidine Deaminase - deficiency; Cytidine Deaminase - genetics; Cytidine Deaminase - metabolism; Genes, Immunoglobulin Heavy Chain; Immune regulation; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Switch Region - genetics; Immunoglobulins; In Situ Hybridization, Fluorescence; Mice; Mice, Transgenic; Molecular immunology; Polymerase Chain Reaction; Recombination, Genetic; Transgenes; Translocation, Genetic
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201041077

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 Sγ switch sequences in the endogenous Igh locus participate in chromosomal translocations with the non‐homolog transgene‐bearing chromosome, Sμ switch sequences do not. This contrasts with the fact that both endogenous Sμ and Sγ sequences participate in intrachromosomal CSR. Our findings suggest the operation of a regulatory mechanism that can differentially control the accessibility of Sμ and Sγ regions for non‐homolog translocations even when both are accessible for intrachromosomal recombination.