Unusual germline DSP2 gene accounts for all apparent V-D-D-J rearrangements in newborn, but not adult, MRL mice

Anti-dsDNA autoantibodies in MRL mice contain a higher than average frequen cy of atypical complementarity-determining regions 3, including those made with D-D rearrangements. It has been reported that MRL mice have an intrins ically high frequency of creating VDDJ rearrangements; however, we show in this study that the majority of these apparent D-D rearrangements in B cell progenitors can be accounted for by a very novel germline D-H gene in mice of the Igh(i) haplotype. This gene has the appearance of a D to D rearrang ement due to the duplication of 9 bp common to most DSP2 genes. Germline DS P2 genes from Igh(i) mice were amplified, cloned, and sequenced, showing th e presence of this novel gene as well as a new allele of a conventional DSP 2 gene. Sequencing of D-J rearrangements revealed that Igh(i) mice also hav e a different allele of DFL16.1 and apparently lack DFL16.2. Despite the ex istence of this new DSP gene, analysis of VDJ rearrangements from adult bon e marrow pre-B cells of MRL/lpr mice still revealed the presence of complem entarity-determining region 3 containing apparent D-D joinings in 4.6% of t he sequences. C3H pre-B cells had 4.2% of sequences with apparent VDDJ rear rangements, and BALB/c pre-B cells had similar to2%. DDJ intermediates were also observed, but at a lower frequency. However, strikingly, no VDDJ rear rangements were observed in newborn sequences, suggesting the process of as sembly of VDJ rearrangements is fundamentally different in newborn mice vs adult mice.