Unusual Germline DSP2 Gene Accounts for All Apparent V-D-D-J Rearrangements in Newborn, But Not Adult, MRL Mice

• Published in: The Journal of immunology (1950) 2001-12, Vol.167 (12), p.6933-6938
• Main Authors: Kompfner, Elizabeth, Oliveira, Paula, Montalbano, Alina, Feeney, Ann J
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Animals, Newborn; Antibodies, Antinuclear - genetics; B-Lymphocytes - immunology; Base Sequence; Complementarity Determining Regions; DSP2 gene; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Germ-Line Mutation; Hematopoietic Stem Cells - immunology; Immunoglobulin Joining Region; Immunoglobulin Variable Region; Lupus Erythematosus, Systemic - genetics; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred MRL lpr
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.12.6933

Anti-dsDNA autoantibodies in MRL mice contain a higher than average frequency of atypical complementarity-determining regions 3, including those made with D-D rearrangements. It has been reported that MRL mice have an intrinsically 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(j) haplotype. This gene has the appearance of a D to D rearrangement due to the duplication of 9 bp common to most DSP2 genes. Germline DSP2 genes from Igh(j) mice were amplified, cloned, and sequenced, showing the presence of this novel gene as well as a new allele of a conventional DSP2 gene. Sequencing of D-J rearrangements revealed that Igh(j) mice also have a different allele of DFL16.1 and apparently lack DFL16.2. Despite the existence of this new DSP gene, analysis of VDJ rearrangements from adult bone marrow pre-B cells of MRL/lpr mice still revealed the presence of complementarity-determining region 3 containing apparent D-D joinings in 4.6% of the sequences. C3H pre-B cells had 4.2% of sequences with apparent VDDJ rearrangements, and BALB/c pre-B cells had approximately 2%. DDJ intermediates were also observed, but at a lower frequency. However, strikingly, no VDDJ rearrangements were observed in newborn sequences, suggesting the process of assembly of VDJ rearrangements is fundamentally different in newborn mice vs adult mice.