International Immunology, Vol. 14, No. 1, 55-64,
January 2002
© 2002 Japanese Society for Immunology
Gene conversion–like sequence transfers in a mouse antibody transgene: antigen selection allows sensitive detection of V region interactions based on homology
1 Immunology and
2 Genetics Programs, and
3 Department of Pathology, Tufts University School of Medicine, Boston, MA 02111, USA
Correspondence to: E. Selsing, Department of Pathology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
Gene conversion is important for antibody diversification in chickens, rabbits and cows. In mice, however, conversion events appear to be infrequent among endogenous antibody genes. DNA sequence transfer events that resemble gene conversions have been reported for a mouse H chain transgene (VVCµ) that contains two closely spaced homologous VDJ segments. Surprisingly, these reported VVCµ sequence transfers were found frequently among mouse B cells responding to immunization. Transgene sequence transfers could be occurring at high frequency in responding VVCµ B cells or could be occurring at lower frequency with subsequent amplification by preferential antigen selection. To distinguish these possibilities, we have analyzed a second transgene (InVVCµ) that is identical to VVCµ except that the two VDJ regions have been exchanged in position. We find that transgene sequence transfers are much less frequent among responding B cells in InVVCµ mice, demonstrating the importance of selection in the frequent transgene conversions observed in VVCµ mice. These results suggest that mice, like other species, can use gene conversion to diversify antibodies. Such diversification events are apparently infrequent, however, and might only be detected among endogenous Ig genes with a favorable arrangement of V genes and an antigenic stimulation that selects cells with conversions. For both VVCµ and InVVCµ mice, conversion-like sequence transfers are strongly correlated with somatic hypermutation. Based on these results, we hypothesize that, in mice, gene conversions represent infrequent alternative reactions of a homology-based DNA repair process that is central in the somatic hypermutational mechanism.
Keywords: B cells, generation of diversity, H chain, Ig, somatic mutation
Transmitting editor: E. A. Clark
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