The immature B-cell subpopulation with low RAG1 expression is increased in the autoimmune New Zealand Black mouse

Eur J Immunol. 2009 Feb;39(2):600-11. doi: 10.1002/eji.200838644.

Abstract

Receptor editing is believed to play a critical role in immunological tolerance by altering the specificity of autoreactive B cells that emerge in the bone marrow. To study whether receptor editing is altered in autoimmune disease, recombination activation gene 1 (rag1) transcription in B cells from New Zealand Black (NZB) mice was examined by introducing a GFP gene at the rag1 locus. Female NZB(RAG1-GFP) mice generated autoantibodies and glomerular immune complexes. NZB(RAG1-GFP) mice did not display increased RAG1-GFP signal in B-1 and B-2 cells from the spleen and peritoneal cavity even following in vitro stimulation compared with C57BL/6(RAG1-GFP) control mice. The early B cells in the bone marrow were classified into RAG1-GFP(-) and RAG1-GFP(+) subpopulations. The RAG1-GFP(-) immature B-cell population was in the minority in C57BL/6(RAG1-GFP) mice but was markedly increased in NZB(RAG1-GFP) mice. RAG1-GFP(-) immature B cells from NZB(RAG1-GFP) mice differentiated into anti-dsDNA Ab-producing cells after stimulation by LPS in vitro. RAG1-GFP(-) immature B cells from NZB(RAG1-GFP) mice displayed a different expression profile of transcription factors required for receptor editing, including pax5 and irf4, in comparison with the RAG1-GFP(+) immature B-cell population. In conclusion, the early B-cell subpopulation, which exhibits low RAG1 expression and presumably concomitantly low receptor editing, was found to be increased in NZB mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / blood
  • Autoimmunity / immunology
  • Female
  • Gene Knock-In Techniques
  • Green Fluorescent Proteins / metabolism
  • Homeodomain Proteins / immunology*
  • Homeodomain Proteins / metabolism
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred NZB
  • Precursor Cells, B-Lymphoid / drug effects
  • Precursor Cells, B-Lymphoid / immunology*
  • Precursor Cells, B-Lymphoid / metabolism

Substances

  • Autoantibodies
  • Homeodomain Proteins
  • Lipopolysaccharides
  • RAG-1 protein
  • Green Fluorescent Proteins