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

Academic Article
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Overview

authors

  • Kompfner, E.
  • Oliveira, P.
  • Montalbano, A.
  • Feeney, Ann

publication date

  • December 2001

journal

  • Journal of Immunology  Journal

abstract

  • 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.

subject areas

  • Age Factors
  • Animals
  • Animals, Newborn
  • Antibodies, Antinuclear
  • B-Lymphocytes
  • Base Sequence
  • Complementarity Determining Regions
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Germ-Line Mutation
  • Hematopoietic Stem Cells
  • Immunoglobulin Joining Region
  • Immunoglobulin Variable Region
  • Lupus Erythematosus, Systemic
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred MRL lpr
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Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 11739512
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Additional Document Info

start page

  • 6933

end page

  • 6938

volume

  • 167

issue

  • 12

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