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 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.
Kompfner
E
E
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Oliveira
P
P
Montalbano
A
A
Feeney
A J
AJ
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000974:Antibodies, Antinuclear / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D022801:Complementarity Determining Regions; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D018095:Germ-Line Mutation; D006412:Hematopoietic Stem Cells / Q000276:immunology; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr
D000974:Antibodies, Antinuclear; D022801:Complementarity Determining Regions; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region