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Sequence Transfers between Variable Regions in a Mouse Antibody Transgene Can Occur by Gene Conversion¹

Nicole D’Avirro^*, David Truong, Bo Xu and Erik Selsing^2,*,,

^* Program in Genetics, Program in Immunology, and Department of Pathology, Tufts University School of Medicine, Boston, MA 02111

Different vertebrate species show widely differing usage of somatic hyperconversion (SHC) as a mechanism for diversifying expressed Ab V genes. The basis for the differing levels of SHC in different species is not known. Although no clear evidence for SHC has been found in normal mouse B cells, transgenic mice carrying high-copy numbers of a gene construct designed to optimize detection of SHC have previously been shown to exhibit sequence transfers that resemble gene conversion events. However, these transgene sequence transfers could reflect multistep or reciprocal DNA recombination events rather than gene conversions. We now find in low-copy number transgenic mice that transgene sequence transfers can exhibit the unidirectional sequence information movement that is a hallmark of gene conversion. This indicates that gene conversion between V region sequences can occur in mouse B cells; we propose that the lack of efficient SHC contributions to Ab diversification in normal mice may be due, at least in part, to the particular pattern of V gene recombinational accessibility that occurs in differentiating mouse B cells.

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