Scientific article

Dysregulated expression of the Cd22 gene as a result of a short interspersed nucleotide element insertion in Cd22a lupus-prone mice

Published inThe Journal of immunology, vol. 165, no. 6, p. 2987-2996
Publication date2000

The Cd22 gene encodes a B cell-specific adhesion molecule that modulates B cell Ag receptor-mediated signal transduction, and is allelic to a lupus-susceptibility locus in New Zealand White (NZW) mice. In this study, we show that, in addition to the wild-type transcripts, NZW (Cd22a) mice synthesize aberrant CD22 mRNAs that contain approximately 20-120 nucleotide insertions upstream of the coding region between exons 2 and 3, and/or approximately 100-190 nucleotide deletions of exon 4. Sequence analysis revealed that these aberrant mRNA species arose by alternative splicing due to the presence in the NZW strain of a 794-bp sequence insertion in the second intron, containing a cluster of short interspersed nucleotide elements. Both the presence of sequence insertion and aberrantly spliced mRNAs were specific to mice bearing the Cd22a and Cd22c alleles. Up-regulation of CD22 expression after LPS activation appeared impaired in Cd22a spleen cells (twice lower than in Cd22b B cells). Furthermore, we show that partial CD22 deficiency, i.e., heterozygous level of CD22 expression, markedly promotes the production of IgG anti-DNA autoantibodies in C57BL/6 (Cd22b) mice bearing the Y chromosome-linked autoimmune acceleration gene, Yaa. Taken together, these results suggest that a lower up-regulation of CD22 on activated B cells (resulting from Cd22 gene anomaly in Cd22a mice or from CD22 heterozygosity in mutants obtained by gene targeting) is implicated in autoantibody production, providing support for Cd22a as a possible candidate allele contributing to lupus susceptibility.

  • Alternative Splicing/immunology
  • Animals
  • Antigens, CD/biosynthesis/ genetics
  • Antigens, CD22
  • Antigens, Differentiation, B-Lymphocyte/biosynthesis/ genetics
  • B-Lymphocytes/immunology/metabolism
  • Base Sequence
  • Cell Adhesion Molecules
  • Exons
  • Gene Expression Regulation/ immunology
  • Immunologic Deficiency Syndromes/genetics
  • Introns
  • Lectins
  • Lipopolysaccharides/immunology
  • Lupus Nephritis/ genetics/ immunology
  • Lymphocyte Activation/genetics
  • Male
  • Mice
  • Mice, Inbred AKR
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Inbred DBA
  • Mice, Inbred MRL lpr
  • Mice, Inbred NZB
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Mutagenesis, Insertional/ immunology
  • RNA Precursors/genetics/metabolism
  • RNA, Messenger/biosynthesis
  • Sequence Deletion
  • Short Interspersed Nucleotide Elements/ immunology
  • Spleen/cytology
  • Up-Regulation/immunology
  • Y Chromosome/immunology
Affiliation Not a UNIGE publication
Citation (ISO format)
MARY, Charles et al. Dysregulated expression of the Cd22 gene as a result of a short interspersed nucleotide element insertion in Cd22a lupus-prone mice. In: The Journal of immunology, 2000, vol. 165, n° 6, p. 2987–2996. doi: 10.4049/jimmunol.165.6.2987
Updates (1)
ISSN of the journal0022-1767

Technical informations

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